| Title of Invention | CHIRAL LIGANDS, METAL COMPLEXES OF TRANSITION METALS COMPRISING THE CHIRAL LIGANDS AND PROCESS THEREOF |
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| Abstract | Ligands of the formula (I) secondary phosphine-Q-P(=O)HR1 (I) in the form of mixtures of diastereomers or pure diastereomers, in which secondary phosphine is a secondary phosphine group with hydrocarbon radicals or heterohydrocarbon radicals as substituents; Q is a bivalent bisaryl or bisheteroaryl radical with an axial chiral centre to which the two phosphorus atoms are bonded in the ortho positions to the bisaryl or bisheteroaryl bridge bond, or Q is a bivalent ferrocenyl radical with a planar chiral centre or without a planar chiral centre, to which the phosphorus atom of the secondary phosphine is bonded directly or via a C1-C4-carbon chain to a cyclopentadienyl ring, the -P*(=O)HR1 group is bonded either on the same cyclopentadienyl ring in ortho position to the bonded secondary phosphine or on the other cyclopentadienyl ring; P* is a chiral phosphorus atom, and R1 is a hydrocarbon radical, a heterohydrocarbon radical or a ferrocenyl radical, where R1 is a ferrocenyl radical with a planar chiral centre when Q is a ferrocenyl radical without a planar chiral centre. Metal complexes of these ligands are homogeneous catalysts for asymmetric addition reactions, particularly hydrogenations. |
| Full Text | CHIRAL LIGANDS USED IN TRANSITION METAL CATYLSTS FOR ASYMMETRIC ADDITION REACTIONS ESPECIALLY HYDROGENATION The present invention relates to ligands having at least two chiral centres and having a backbone which is (a) a chiral aromatic or heteroaromatic atropisomer or (b) an achiral or chiral planar-isomeric metallocene, to which are bonded in each case one -PR2 group and one P-chiral -P(0)HR group, where, in the case of an achiral ' metallocene as the backbone, the R radical in the -P(0)HR group contains at least one chiral centre; to processes for their preparation; to metal complexes of these bidentate ligands with transition metals; and to the use of the metal complexes in asymmetric syntheses, particularly in hydrogenations with hydrogen of prochlral organic compounds which contain at least one carbon/caiton or carbon/heteroatom double bond. Metal complexes with chiral ligands have been found to be valuable catalysts in asymmetric syntheses. Those metal complexes with which not only sufficient catalytic activity but also high stereoselectivity can be achieved are of practical use. Without these two properties, there is no scale-up to industrial processes for economic reasons. To date, it is still not possible to forecast which metal complexes with which ligands under which reaction conditions for which unsaturated substrates give rise to practically usable hydrogenation results with regard to the catalytic activity and stereoselectivity. A multitude of different bidentate ligands has therefore been provided, which may contain chelating groups with oxygen, sulphur, nitrogen and/or phosphorus atoms (see, for example, W. Teng, X. Zhang, Chem. Rev. 2003,103, 3029-3069). Among these bidentate ligands, P'^N and P'^P ligands have frequently been found to be useful, particularly when the chelating groups are bonded to aromatics with atropisomerism (bisarenes and bisheteroarenes) or planar isomerism (metallocenes). In recent times, a monodentate phosphine oxide benzene of the formula A and bidentate ligands of the formula B have also been described [see thesis by Xiaobin Jiang with Prof. J.G. de Vries and Prof, B.L. Feringa, University of Groningen 29 Nov. 2004 (ISBN: 90-367-2144X); Xiaobin Jiang et al., Org. Lett.. 5 (2003) 1503-6; and Xiaobin Jiang et al., Tetrahedron: Asymmetry, 15 (2004) 2223-9]: C(CH3)3 C(CH3)3 H H ^ (A) (B), The preparation of these llgands is complicated. The synthesis generally affords racemates which are subsequently separated into their enantiomers, usually with the aid of preparative high-pressure chromatography on chiral columns. This method is very expensive and unsuitable for production on a larger scale. Alternatively, in a few cases, the enantiomers have been separated as an adduct with a chiral auxiliary reagent by selective crystallization. However, this route is too often unsuccessful. Since generally only one of the two enantiomers is required for practical applications, at least half of the desired llgand is also always lost in these methods. The llgands of the formula A have been used In Ir and Rh complexes for the asymmetric hydrogenation of prochiral imines and alkenes, and good stereo¬selectivities but low catalyst activities [turnover frequency (TOP) There Is a great need for further ligands which have a secondary phosphlne and phosphine oxide group bonded on the backbone, which can be prepared in a simple manner and which are also suitable as ligands for metal complexes in asymmetric catalysts. It has now been found that, surprisingly, the preparation of optically pure isomers with a secondary -P(0)HR group bonded on the backbone and a -PR2 group bonded on the backbone, optionally via carbon atoms, succeeds In a particularly simple manner when the backbone is an aromatic with axial chiraiity, or the ligand contains at least one chiral metallocene. The presence of a further optical centre as well as the chiral secondary phosphine oxide group leads, In the synthesis of the bidentate ligands, oft^n to excellent diastereoselectivities and additionally allows simple purification or separation of the stereoisomers by crystallization or by preparative chromatography on achiral columns. It has also been found that, surprisingly, these ligands have an unexpectedly great influence on the catalytic properties and, compared to the known ligand B in metal complexes, frequently feature surprisingly high catalytic activities as catalysts, and, depending on the prochiral substrate, very good to very high stereoselectivities can also be achieved. The invention firstly provides compounds of the formula I having at least two chiral centres in the form of mixtures of diastereomers or pure diastereomers secondary phosphine-Q-P*(=0)HRi (I), in which secondary phosphine is a secondary phosphine group with hydrocarbon radicals or heterohydrocarbon radicals as substituents; Q is a bivalent bisaryl or bisheteroaryl radical with an axial chiral centre to which the two phosphorus atoms are bonded in the ortho positions to the bisaryl or bishetero¬aryl bridge bond, or Q is a bivalent ferrocenyl radical with a planar chiral centre or without a planar chiral centre, to which the phosphorus atom of the secondary phosphine is bonded directly or via a Ci-C4-carbon chain to a cyclopentadienyl ring, the -P*(=0)HRi group is bonded either on the same cyclopentadienyl ring In ortho position to the bonded secondary phosphine or on the other cyclopentadienyl ring; P* is a chiral phosphorus atom, and Ri is a hydrocarbon radical, a heterohydrocarbon radical or a fen"ocenyl radical, where Ri is a ferrocenyl radical with a planar chiral centre when Q as a ferrocenyl radical does not have a planar chiral centre. In the context of the present invention, a "chiral centre" can be a planar chiral centre, an axial chiral centre or an atom-centred chiral centre, in which case the atom is preferably C or P. The compounds of the formula I have usually 2 to 5, preferably 2 to 4 and more pre¬ferably 2 or 3 chiral centres. The compounds of the formula I may, for example, in substituents of the aromatic radicals, in substituents on the cyclopentadienyl in the ferrocene or in the C1-C4- carbon chain, contain at least one asymmetric carbon atom as a further chiral centre. For explanation, it is noted that the compounds of the formula I also include the tautomeric form in which the -P*(=0)HRi group is represented as the hydroxyl form -P*(OH)Ri. In the two tautomeric forms, the phosphorus atom is asymmetric and chiral. The bridging group Q may be unsubstituted or substituted by substituents Rx such as halogen or a hydrocarbon radical bonded via a carbon atom, oxygen atom, sulphur atom or silicon atom, for example one to six times, preferably one to four times and more preferably once to twice, where hydrocart)on radicals in substituents R* may In turn be substituted. When the bridging group Q Is a bisaryl or bisheteroaryl radical, it can also be provided with ring-bonding substituents, for example alkylene, alkenylene, alkdlenylene, alkylenediamino or alkylenedioxy. When at least two substituents are bonded in the Q group, they may be the same or different. The optionally substituted substituent R* may, for example, be Ci-Ci2-alkyl, pre¬ferably Ci-Cs-alkyl, and more preferably Ci-C4-alkyl. Examples are methyl, ethyl, n- or i-propyl, n-, I- or t-butyl, pentyl, hexyl, octyl, decyl, undecyl and dodecyl. The optionally substituted substituent R* may, for example, be Cs-Cs-cycloalkyI, preferably Cs-Ce-cycloalkyl. Examples are cyclopentyl, cyclohexyl and cyclooctyl. The optionally substituted substituent Rx may, for example, be Cs-Cs-cycloalkylalkyI, preferably Cs-Ce-cycloalkylalkyl. Examples are cyclopentylmethyl, cyclohexylmethyl or -ethyl and cyclooctylmethyl. The optionally substituted substituent R* may, for example, be Ce-Cia-aryl and pre¬ferably Ce-Cio-aryl. Examples are phenyl or naphthyl. The optionally substituted substituent Rx may, for example, be C7-Ci2-aralkyl (for example benzyl or 1-phenyleth-2-yl). The optionally substituted substituent Rx may, for example, be tri(Ci-C4-alkyl)Si or triphenylsilyl. Examples of trialkylsilyl are trimethyl-, triethyl-, tii-n-propyl-, tri-n-butyl- and dimethyl-t-butylsilyl. The substituent R* may, for example, be halogen. Examples are F, CI and Br. The optionally substituted substituent Rx may, for example, be an alkoxy radical, thio radical, sulphoxide or a sulphone radical of the formulae -ORos, -SR05, -S(0)Ro5 and -S(0)2Ro5. in which R05 is Ci-Ci2-alkyl, preferably Ci-Ca-alkyl and more preferably Ci-C4-alkyl; Cs-Ce-cycloalkyl. preferably Cs-Ce-cycloalkyI; Ce-Cia-aryl and preferably Ce-Cio-aryl; or CrCi2-aralkyl. Examples of these hydrocarbon radicals have already been mentioned above for the substituents. The substituent R* may, for example, be -CH(0). -C(0)-Ci-C4-alkyl or -C(0)-C6-Cio- aryl. The optionally substituted substituent Rx may, for example, be -CO2R03 or -C(0)-NROIRO2 radicals in which R01, R02 and R03 are each independently C1-C12- alkyl, Cs-Ce-cycloalkyl, Cs-Ce-cycloalkylmethyl or -ethyl, unsubstituted or Ci-C4-alkyl- or Ci-C4-alkoxy-substltuted Cg-Cto-aryl or C7-Ci2-aralkyl, or R01 and R02 together are trimethylene, tetramethylene, 3-oxa-1,5-pentylene or3-(Ci-C4-?ilkyl)amino-1,6- pentylene. R01, R02 and R03 may, as alkyi, be linear or branched, and the alkyi contains preferably 1 to 8 and more preferably 1 to 4 carbon atoms. Roi, R02 and R03 may, as aryl, for example, be phenyl or naphthyl and, as aralkyi, be benzyl or phenyl- ethyl. Some examples of Roi. R02 and R03 are methyl, ethyl, n- or i-propyl, n-, I- or t- butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, phenyl, benzyl, methylphenyl, methylbenzyl, methoxyphenyl, dimethoxyphenyl and methoxybenzyl. The optionally substituted substituent R* may, for example, be -S(0)-0-Ro3, -S(0)2-0-RO3, -S(0)-NROIRO2 and -S(0)2-NRoiRo2 radicals, in which Roi, Ro2and R03 are each as defined above, including the preferences. When Q is the bivalent radical of a bisaryl or bisheteroaryl with monocyclic aromatics, preferably one or both of the other ortho positions to the bond (bridge bond) which joins the two monocyclic aromatics are substituted in order to prevent free rotation. In this case, prefen-ed substituents are Ci-Ci2-alkyl, preferably Ci-Ce-alkyl and more preferably Ci-C4-alkyl; Cs-Ca-cycloalkyI, preferably Cs-Ce-cycloalkyI; Ce-Cia-aryl and preferably Ce-Cio-aryl; or C7-Ci2-aralkyl; Ci-Ci2-alkoxy, preferably Ci-Ce-alkoxy and more preferably Ci-C4-a[koxy; Cs-Cs-cycloalkoxy, preferably Cs-Ce-cycloalkoxy; Ce-Cie-aryloxy and preferably Ce-Cio-aryloxy; or CrCi2-aralkyloxy; Ci-Ci2-alkylthio, preferably Ci-Ce-alkylthio and more preferably Ci-ChalkyIthio; Cs-Ce-cycloalkylthio, preferably Cs-Ce-cycloalkylthio; Ce-Cis-arythiol and preferably Ce-Cio-arylthio; or C7-Ci2-aralkylthio, and tri-Ci-Ce-alkylsilyl. When Q is the bivalent radical of a bisaryl or bisheteroaryl with monocyclic aromatics, it is also possible for bivalent substituents to be bonded, in the case of bisaryls to two adjacent carbon atoms, particularly in the 5,6 and/or 5',6' positions (fused rings) or in the 6,6' positions. The bivalent substituents may be (ji),a)'-Ci- to -Ce-alkylene, Ci- to -Ce-alkylene-O", Ci- to -C6-alkylene-N(Ci-C4-alkyl)-. -0-(Ci- to -C6-alkylene)-0-, -(Ci-C4-alkyl)N(Ci- to -C6-alkylene)-N(Ci-C4-alkyi)-, -0-(Ci- to -C6-alkylene)-N(Ci-C4- alkyl)-, -CH2-CH=CH-, -0-CH=CH-, -S-CH=CH-, -N(Ci-C4-alkyl)-CH=CH-. -CH=CH-CH=CH-, -CH=CH-CH=N-. -CH=CH-N=CH-, -CH=N-CH=CH-, -N=CH-CH=CH-. -CH=N-CH=N-, -N=CH-CH=N-, and -CH=N-N=CH-. The hydrocarbon radicals of the substituents Rx may in turn be mono- or polysub- stituted, for example mono- to trisubstituted, preferably mono- or disubstituted, for example by halogen (F, CI or Br, particularly F), -OH, -SH, -CH(0), -CN. -NR001R02. -C(0)-0-ROO3. -S(0)-0-ROO3. -S(0)2-0-ROO3. -P(ORO3)2. -P(0)(OROO3)2, -C(0)-NROOIROO2, -S(0)-NROOIRO2, -S(0)2-NROOIROO2. -0-(0)C-ROO4. -ROOIN-(0)C-ROO4, -ROOIN-S(0)-ROO4. -ROOIN-S(0)2-ROO4. Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-alkylthio, Cs-Ce-cycloalkyl. phenyl, benzyl, phenoxy or benzyloxy, where R001 and R002 are each independently hydrogen, Ci-C4-alkyl, cyclopentyl, cyclohexyl, phenyl, benzyl or R001 and R002 together are tetramethylene, pentamethylene or 3-oxapentane-1,5-diyl, R003 is hydrogen, Ci-Ce- alkyl, Cs-Ce-cycloalkyl, phenyl or benzyl, and Roo4 is Ci-Ci8-alkyl and preferably Ci-Ci2-alkyl, Ci-C4-haloalkyl, Ci-C4-hydroxyalkyl, Cs-Ca-cycloalkyl (for example cyclopentyl, cyclohexyl), Ce-Cio-aryl (for example phenyl or naphthyl) or Cr-Ciraralkyl (for example benzyl). The bivalent Q radical in formula I may be radicals in which two hydrocarbon aromatics, two heteroaromatics or one hydrocarbon aromatic and one hetero- aromatic are bonded to one another. In fused heteroaromatics with five-membered heteroaromatic rings, the heteroaromatic rings and preferably the hydrocarbon rings may be joined. Examples of hydrocarbon aromatics are in particular benzene, indene and naphthalene. Examples of heteroaromatics and fused heteroaromatics are fiiran, benzofuran, thiophene, benzothiophene, N-(Ci-C4-alkyl)pyn'ole, N(Ci-C4-alkyl)indole, pyridine, quinoline and isoquinoline. Preferred bivalent Q radicals of bisarylene or -heteroarylene are those of the fomiulae II and lla (II) ^^ (lla) in which one or both Rz are a substituent or part of a fused ring, and the rings together with the carbon atoms bonded to them form optionally fused 5- or 6-membered aromatic or heteroaromatic rings which are unsubstituted or mono- or polysubstituted. in which Xi is O. S or N(Ci-C4-alkyl); In a preferred embodiment of the Invention, the bivalent Q radical in formula I, as bisaryl or bisheteroaryl, corresponds to the fonnulae III. IV, V or VI R4, Rs, Re and R7 are each independently hydrogen, Ci-Cs-alkyl, Cs-Cs-cycloalkyI, Ci-Ce-alkoxy, CrCe-alkylthio, Ci-Cs-hydroxyaikyl, C2-C8-hydroxyalkoxy, Ci-Ce- alkoxy-Ci-Ce-alkyl, Ci-C4-alkoxy-Ci-C8-alkoxy, Ce-Cio-aryl, C7-Ci2-aralkyl, -OCF3 or -CF3, where at least one of R5 is a substituent, or R4 and Rs together are trimethylene, tetramethylene, -CH2-CH=CH-, -CH=CH- CH=CH-, -0-CH=CH-. -S-CH=CH-, -N(Ci-C4-alkyl)-CH=CH-. -O-CH2-O-, -O-CF2-O-. -O-CH2-CH2-O-, -N(Ci-C4-alkyl)-CH2-CH2-0-, or the R5 radicals together are Ci-Ce- alkylene or -0-(Ci-C6-alkylene)-0-. In the bivalent radicals of the formulae III, IV, V and VI, further hydrogen atoms may be substituted, for example by radicals as defined for R4, R5, Re and R7. The aromatic and heteroaromatic rings may contain further substituents as defined above. A preferred subgroup is that of compounds of the formula III In which Rs is C1-C4- alkyl (for example methyl, ethyl, n- and i-propyl, n-, i- and t-butyl), Ci-C4-alkoxy (for example methoxy, ethoxy, n- or l-propoxy, butoxy), Ci-C4-hydroxyalkyl (for example hydroxymethyl, hydroxyethyl), C2-C4-hydroxyalkoxy (for example hydroxyethyloxy, hydroxypropyloxy), Ci-C4-alkoxy-Ci-C2-alkyl (for example methoxymethyl, ethoxy- methyl, methoxyethyl, ethoxyethyl), Ci-C4-alkoxy-Ci-C2-alkoxy (for example methoxymethoxy, methoxyethoxy, ethoxymethoxy), trifluoromethyl or trimethylsilyl; R4 and Rs together are trimethylene, tetramethylene, -CH2-CH=CH-, -CH=CH- CH=CH-, -O-CH2-O-, -O-CF2-O-, -O-CH2-CH2-O-. -N(Ci-C4-alkyl)-CH2-CH2-0- or benzene-1,2-dioxy, or the R5 radicals together are C2-C6-alkylene, -0-(Ci-C4- alkylene)-0- or -O-CF2-O-. In another preferred embodiment of the invention, the bivalent Q radical in formula I, as a ferrocenyl radical with a planar chiral centre, corresponds to the radicals of the fomiulae VII, VIII and IX © .. ^ ... f - (VII) ^ (VIII) ' (IX) or a fennocenyl radical without a planar chiral centre of the formula XX ? (XX) in which R9 is Ci-Ca-alkyI, Cs-Cs-cycloalkyI, phenyl, benzyl or methylbenzyl; Rio is vinyl, methyl, ethyl, a C-bonded chiral group which directs metals of metallating reagents into the ortho position, or Rio is a -CH2-NR11R12 group; Rg is preferably Ci-C4-alkyl, cyclopentyl, cyclohexyl, phenyl, benzyl or methylbenzyl; or R11 arid R12 are each independently Ci-Cs-alkyl, Cs-Cs-cycloalkyl, Ce-Cio-aryl, C7-Ci2-aralkyl. C7-Ci2-alkaryl, orC8-Ci2-alkaralkyl, or Rn and R12 together are tetramethylene, pentamethylene or 3-oxapentane-1,5-diyl. R9 is more preferably methyl, ethyl or phenyl. Rii and R12 are preferably identical radicals. Rn and R12 are preferably each C1-C4- alkyl, cyclopentyl, cyclohexyl, phenyl, methylphenyl, methylbenzyl or benzyl, or Rn and Ri2 together are preferably tetramethylene or 3-oxapentane-1,5-diyl. More preferably, Rn and R12 are each methyl or ethyl. In the ortho-directing chiral Rio group, the chiral atom is preferably bonded in the 1, 2 or 3 position to the cyclopentadienyl-Rio bond. The Rio group may be open-chain radicals or cyclic radicals, the atoms being selected from the group of H, C, O, S and N. The Rio group may, for example, correspond to the formula -HC*Ri4Ri5 (* indicates the asymmetric atom) in which R14 is Ci-Ce-alkyl, Cs-Ca-cycloalkyI (cyclohexyl), Ce-Cio-aryl (phenyl), C7-Ci2-aralkyl (benzyl) or C7-Ci2-alkaralkyl (methylbenzyl), R15 is -OR16 or -NR11R12, RI6 is Ci-Cs-alkyI, Cs-Cs-cycloalkyI, phenyl or benzyl, and Rn and Ri2 are the same or different and are each Ci-Cs-alkyI, Cs-Ce-cycloalkyI, phenyl or benzyl, or Rn and R12 together with the nitrogen atom form a five- to eight- membered ring. R14 is preferably Ci-Ce-alkyI, for example methyl, ethyl, n-propyl, or phenyl. Rie is preferably Ci-C4-alkyl, for example methyl, ethyl, n-propyl and n- or l-butyl. R11 and R12 are preferably identical radicals and are preferably each C1-C4- alkyl, for example methyl, ethyl, n-propyl, i-propyl and n- or i-butyl, and together tetramethylene, pentamethylene or 3-oxa-1,5-pentylene. Particularly preferred groups of the formula -HCR14R15 are 1-methoxyeth-1-yl, 1-dimethylaminoeth-1-yl and 1 -(dimethylamino)-l -phenylmethyl. When R10 is a radical without a chiral a-carbon atom, It is bonded to the cyclo- pentadienyl ring via a carbon atom either directly or via a bridge group. The bridge group may, for example, be methylene, ethylene or an imine group. Cyclic radicals bonded to the bridge group are preferably saturated and are more preferably C1-C4- alkyl-, (Ci-C4-alkyl)2NCH2-. (Ci-C4-alkyl)2NCH2CH2-, Ci-C4-alkoxymethyl- orCi-C4- alkoxyethyl-substituted N-, O- or N,0-heterocycloalkyl having a total of 6 or 6 ring atoms. Open-chain radicals are preferably bonded to the cyclopentadienyl ring via a CH2 group and the radicals derive preferably from amino acids or ephedrine. Some preferred examples are: CH3 —C=N—N' o. N- -CHj—N. N r • Ri7 * I Ri7 CH3 CH3 * / O—V R,7 -H,C—N-CH CH3O In which R17 is Ci-C4-alkyl. (Ci-C4-alkyl)2NCH2-, (Ci-C4-alkyl)2NCH2CH2-. C1-C4- alkoxymethyl or Ci-C4-alkoxyethyl. More preferably R17 is methoxymethyl or dimethyiamlnomethyl. CH, CH3 V -H2C—N-CH and —CgHg may be Radicals of the formulae CH3O converted In a simple manner by means of substitution to preferred -CH2-NR11R12 groups. Ri7 In a prefen-ed embodiment. Rio is -CH2-NR11R12, -CHR9-NR11R12, vinyl, methyl or ethyl, where R9 is methyl, ethyl or phenyl, and Rn and R12 are each methyl or ethyl. The secondary phosphlne group may contain two Identical or different hydrocarbon radicals or heterohydrocarbon radicals. The secondary phosphlne group preferably contains two identical hydrocarbon radicals or heterohydrocarbon radicals. The hydrocarbon radicals and heterohydrocarbon radicals In the secondary phosphlne group may be unsubstituted or substituted and/or contain heteroatoms selected from the group of O, S, -N= or N(Ci-C4-alkyl). They may contain 1 to 30, preferably 1 to 20 and more preferably 1 to 12 carbon atoms. The hydrocarbon radical may be selected from the group of linear or branched Ci-Ci8-alkyl; unsubstituted or Ci-Ce-alkyI- or Ci-Ce-alkoxy-substltuted C5-Ci2-cycloalkyl or C5-C12- cycloalkyI-CH2-; phenyl, naphthyl, furyl or benzyl; or halogen-, Ci-Ce-alkyI-, tri- fluoromethyl-, Ci-Ce-alkoxy-, trlfluoromethoxy-, (C6H5)3Si, (Ci-Ci2-alkyl)3Si or secondary amino-substituted phenyl, naphthyl, furyl or benzyl. Examples of P substltuents as alkyi, which preferably contains 1 to 6 carbon atoms, are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, and the isomers of pentyl and hexyl. Examples of P substltuents as optionally alkyl-substituted cycloalkyi are cyclopentyl, cyclohexyl, methyl- and ethylcyclohexyl, and dimethylcyclohexyl. Examples of P substituents as alkyI- and alkoxy-substituted phenyl and benzyl are methylphenyl, dimethylphenyl, trimethylphenyl, ethylphenyl, methylbenzyl, methoxy- phenyl, dimethoxyphenyl, trimethoxyphenyl, trifluoromethylphenyl, bis(trifluoromethyl)phenyl, tris(trifluoromethyl)phenyl, trifluoromethoxyphenyl, bis(trifluoromethoxy)phenyl, fluoro- and chlorophenyl and 3,5-dimethyl- 4-methoxyphenyl. Prefen'ed secondary phosphine groups are those which contain Identical radicals selected from the group of Ci-Ce-alkyI, unsubstituted cyclopentyl or cyclohexyl or cyclopentyl or cyclohexyl substituted by 1 to 3 Ci-C4-alkyl or Ci-C4-alkoxy, benzyl and particularly phenyl, which are unsubstituted or substituted by 1 to 3 Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-fluoroalkyl or Ci-C4-f1uoroalkoxy, F and CI. The secondary phosphine group corresponds preferably to the formula -PR2R3 in which R2 and R3 are each independently a hydrocarbon radical which has 1 to 18 carbon atoms and Is unsubstituted or substituted by Ci-Ce-alkyI, trifluoromethyl, Ci-Ce-alkoxy, trlfluoromethoxy, (Ci-C4-alkyl)2amino, (C6H5)3Si, (Ci-Ci2-alkyl)3Si, halogen and/or O heteroatoms. R2 and R3 are preferably each radicals selected from the group of linear or branched Ci-Ce-alkyI, unsubstituted cyclopentyl or cyclohexyl or cyclopentyl or cyclohexyl substituted by one to three Ci-C4-alkyl or Ci-C4-alkoxy, furyl, unsubstituted benzyl or benzyl substituted by one to three Ci-C4-alkyl or Ci-C4-alkoxy, and in particular unsubstituted phenyl or phenyl substituted by one to three F, CI, Ci-C4-alkyl, C1-C4- alkoxy, Ci-C4-fluoroalkyl or Ci-C4-fluoroalkoxy. More preferably, R2 and R3 are each radicals selected fjiom the group of Ci-Ce-alkyI, cyclopentyl, cyclohexyl, furyl and unsubstituted phenyl or phenyl substituted by one to three F, CI, Ci-C4-alkyl. Ci-C4-alkoxy and/or Ci-C4-fluoroalkyl. When R2 and Rs in the -PR2R3 group are different, the phosphorus atom of the secondary phosphine group is a further chiral centre. which are unsubstituted or mono- or polysubstituted by Ci-Cs-alkyI, C4-C8-cycloalkyl, Ci-Ce-alkoxy, Ci-C4-alkoxy-Ci-C4-alkyl, phenyl, Ci-C4-alkyl- or Ci-C4-alkoxyphenyl, benzyl, Ci-C4-alkyl- or Ci-C4-alkoxybenzyl, benzyloxy, Ci-C4-alkyl- or Ci-C4-alkoxy- benzyloxy or Ci-C4-alkylidenedioxy. The substituents may be bonded in one or both a positions to the phosphorus atom in order to introduce chrrai carbon atoms. The substituents in one or both a positions are preferably Ci-C4-alkyl or benzyl, for example methyl, ethyl, n- or i-propyl, benzyl or -CH2-0-Ci-C4-alkyl or -CH2-0-C6-Cio-aryl. The secondary phosphine group may be cyclic secondary phosphine. for example those of the formulae Substituents in the p.y positions may, for example, be Ci-C4-all An aliphatic 5- or 6-membered ring or benzene may be fused onto two adjacent carbon atoms in the radicals of the above formulae. The cyclic secondary phosphino may, for example, correspond to the formulae (only one of the possible diastereomers is given) •b R" , "0 CH, J ^ —p > k- -to 7 I 4 -b -b —p in which the R' and R" radicals are each Ci-C4-alkyl, for example methyl, ethyl, n- or i-propyl, benzyl, or -CH2-0-Ci-C4-alkyl or -CH2-0-C6-Cio-aryl, and R' and R" are identical or different from one another. In the compounds of the formula I, secondary phosphine Is preferably a noncyclic secondary phosphine selected from the group of -P(Ci-C6-alkyl)2, -P(C5-C8-cycloalkyl)2. -P(C7-C8-bicycloalkyl)2. -P(o-furyl)2, -P(C6H5)2, -P[2-(Ci-C6-alkyl)C6H4]2, -P[3-(Ci-C6- alkyl)C6H4]2. -P[4-(Ci-C6-alkyl)C6H4]2. -P[2-(Ci-C6-alkoxy)C6H4l2. -P[3-(Ci-C6- alkoxy)C6H4j2. -P(4-(Ci-C6-alkoxy)C6H4]2. -Pl2-(trlfluoromethyl)C6H4l2. -P[3-(trifluoro- methyl)C6H4]2. -P[4-(trifluoromethyl)C6H4]2. -P[3.5-bis(trifluoromethyl)C6H3]2, -P[3,5- bis(Ci-C6-alkyl)2C6H3l2, -PI3.5-bis(Ci-C6-alkoxy)2C6H3]2 and -Pf3.5-bis(Ci-C6-alkyl)2-4- (Ci-C6-alkoxy)C6H2]2. or a cyclic phosphine selected from the group of which are unsubstituted or mono- or polysubstituted by Ci-C4-alkyl, Ci-C4-alkoxy. Ci-C4-alkoxy-Ci-C2-alkyl, phenyl, benzyl, benzyloxy or Ci-C4-alkylidenedioxy. Some specific examples are -P(CH3)2. -P(i-C3H7)2, -P(n-C4H9)2, -P(i-C4H9)2, -P(t-C4H9)2, -P(C5H9). -P(C6Hii)2. -P(norbomyl)2. -P(o-furyl)2, -P(C6H5)2. P[2-(methyl)C6H4l2, P[3-(methyl)C6H4l2. -P[4-(methyl)C6H4]2. -P[2-(methoxy)C6H4]2. -P[3-(methoxy)C6H4]2. -P[4-(methoxy)C6H4]2. -P[3-(trifluoromethyl)C6H4j2, -P[4-(trrfluoromethyl)C6H4]2. -P[3,5-bis(trifluoromethyl)C6H3l2. -P[3,5-bis(methyl)2C6H3]2, -P(3.5-bis(methoxy)2C6H3l2 and -P[3,5-bis(methyl)2-4-(methoxy)C6H2]2. and those of the formulae -P^O R" ^0.0, in which R' is methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, methoxymethyl, ethoxy- methyl or benzyloxymethyl and R" independently has the same definition as R' and is different from R'. The Ci-C4-carbon chain to which the secondary phosphine may be bonded is pre¬ferably an unsubstituted or Ci-Ce-alkyI-, benzyl-, phenyl-, cyclopentyl- or cyclohexyl- substituted alkylene group having 1 to 3 and preferably 1 or 2 carbon atoms. The alkylene group preferably corresponds to the fonnula -CHRs- in which Ra is hydrogen, Ci-C4-alkyl, cyclohexyl or phenyl. When Q is a ferrocene backbone without chirality, Ri must necessarily contain at least one chiral centre. When Q is a fen-ocene backbone with chirality, Ri may be chiral. When Ri is a hydrocarbon radical or a heterohydrocarbon radical, these radicals have the same definitions and preferences as the above-defined substituents in the secondary phosphine group or Ra in the -PR2R3 group. Ri may be selected from the group of linear or branched Ci-Cia-alkyI; unsubstituted or Ci-Ce-alkyI- or Ci-Ce- alkoxy-substituted C5-Ci2-cycloaIkyl or C5-Ci2-cycloalkyl-CH2-; phenyl, naphthyl, furyl or benzyl; or halogen-, Ci-Ce-alkyI-, trifluoromethyl-, Ci-Ce-alkoxy-, trifluoromethoxy-, (C6H5)3Si-, (Ci-Ci2-alkyl)3Si- or secondary amino-substltuted phenyl, naphthyl, fiiryl or benzyl. Ri may preferably be Ci-Ca-alkyI and more preferably Ca-Cs-alkyI, unsub¬stituted cyclopentyl or cyclohexyl, or cyclopentyl or cyclohexyl substituted by 1 to 3 Ci-C4-alkyl or Ci-C4-alkoxy, benzyl and phenyl which are unsubstituted or substituted by 1 to 3 Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-fluoroalkyl or Ci-C4-fluoroalkoxy, F and CI. Among the Cs-Cs-alkyI groups, preference is given to those which are branched in the a position. When Ri is a fennocenyl radical, this radical may be unsubstituted or mono- or polysubstituted. This radical is preferably substituted by an ortho-directing group on the same cyclopentadiene ring in the ortho position to the bonded P*. This ortho- directing group may be vinyl, methyl, ethyl, a C-bonded chiral group which directs metals of metallating reagents into the ortho position, or a -CH2-NR11R12 group. This ortho-directing group is preferably a chiral group, for example of the fomiula -HC*Ri4Ri5 r indicates the asymmetric atom) in which R14 is Ci-Ca-alkyI, Cs-Ca- cycloalkyl (cyclohexyl), Ce-Cio-aryl (phenyl), C7-Ci2-aralkyl (benzyl) or CrCi2-alkaryl (methylbenzyl), R15 is -ORie or-NRiiRi2. Rie is Ci-Ca-alkyI, Cs-Cs-cycloalkyI, phenyl or benzyl, and Rn and R12 are the same or different and are each Ci-Ca-alkyI, Cs-Cs- cycloalkyl, phenyl or benzyl or Rn and R12 together with the nitrogen atom fonn a five- to eight-membered ring. R14 is preferably Ci-C4-alkyl, for example methyl, ethyl, n-propyl and phenyl. Rie is preferably Ci-C4-alkyl, for example methyl, ethyl, n-propyl and n- or i-butyl. Rn and R12 are preferably Identical radicals and are preferably each Ci-C4-alkyl, for example methyl, ethyl, n-propyl, i-propyl and n- or i-butyl, and to¬gether tetramethylene, pentamethylene or 3-oxa-1,5-pentylene. Particulariy preferred groups of the fomiula -HCR14R15 are 1-methoxyeth-1-yl, 1-dimethylaminoeth-1-yl and 1 -(dimethylamino)-l -phenylmethyl. A preferred subgroup of inventive compounds is that of those of the formulae ilia Vila, Villa, IXa and XXa (Vila). ^ (Villa), '^^^^'^(IXa). XXa, In which the 3,3' and/or 4,4* positions In formula Ilia may be substituted by Ci-C4-alkyl, CrC4- alkoxy, trifluoromethyl or trimethylsilyl; Ri Is Ci-Ca-alkyI, unsubstltuted cyclopentyl or cyclohexyl or cyclopentyl or cyclohexyl substituted by 1 to 3 CrC4-alkyl or Ci-C4-alkoxy. or benzyl and phenyl which are unsubstltuted or substituted by 1 to 3 Ci-C4-alkyl, Ci-C4-alkoxy, CrC4-fluoroalkyl or Ci-C4-fIuoroalkoxy, F and CI; Ra and R3 are each independently a hydrocarbon radical which has 1 to 18 carbon atoms and is unsubstltuted or substituted by CrCe-alkyl, trifluoromethyl, Ci-Ce- alkoxy, trifluoromethoxy, (Ci-C4-alkyl)2amino, (C6H5)3Si, (Ci-Ci2-alkyl)3Si, halogen, and/or O heteroatoms; R4 is hydrogen or independently as defined for R5; Rs Is Ci-C4-alkyl. Cf-C4-alkoxy, Ci-C4-hydroxyalkyl, C2-C4-hydroxyalkoxy. C1-C4- alkoxy-Ci-Ca-alkyl, Ci-C4-alkoxy-Ci-C2-alko)cy, trifluoromethyl or trimethylsilyl, or R4 and Rs together are -CH=CH-CH=CH-, trimethylene, tetramethylene, -O-CH2-O-, -O-CF2-O-. -O-CH2-CH2-O-. -N(methyl)-CH2-CH2-0-: PRA the Rs radicals together are C2-C6-alkylene, -0-(Ci-C4-alkylene)-0- or -O-CF2-O-; Hal is CI, Br or 1, and X2 is CI, Br, I, Ci-C4-alkoxy or (Ci-C4-alkyl)2amino, and the compound of the formula XII fomied secondary phosphine-Q-PXaRi (XII) is hydrolysed with water to give a compound of the formula I. .A:: Compounds of the fomnula X are known or can be prepared by known or analogous processes. Ferrocenes of the formula XIII -Rio RjRgP^'^Hal (XIII) can be prepared analogously to the method described by M. Steurer et al. in Chem. Commun., 2005, 4929-4931, by halogenating, for example bromlnating, a ferrocene with the substituent Rio in the ortho position, lithiating the halogenated fenrocene in the ortho position to the halogen by reacting with a lithium secondary amide (Li-NR2), and then reacting the llthiated ferrocene with a halophosphine Hal-PRzRs. Compounds in which Rio is vinyl, ethyl or the -CH2-NR11R12 group are prepared by modifying the Rio group as a C-bonded chiral group which directs metals of metallating reagents into the ortho position after the halogenation, for example by eliminating the chiral auxiliary group to the vinyl group and subsequently hydro- genating it to the ethyl group. The -CH2-NR11R12 group is obtained by substituting a CH2-bonded chiral auxiliary group by HNR11R12. The process conditions for organometailic syntheses are known and will not be described here In detail. Details can be taken from the examples. The inventive compounds of the formula I are ligands for metal complexes selected from the group of the transition metals, which are excellent catalysts or catalyst precursors for asymmetric syntheses, for example the asymmetric hydrogenation of prochiral unsaturated organic compounds. When prochlral unsaturated organic compounds are used, a very high excess of optical isomers can be induced in the synthesis of organic compounds, and a high chemical conversion can be achieved in short reaction times. The achievable enantioselectivitles and catalyst activities are excellent. Moreover, such llgands can also be used in other asymmetric addition or cyclization reactions. The invention further provides metal complexes of transition metals of the transition groups of the Periodic Table of the Elements with a compound of the formula I as a ligand. Among the transition metals, metals are more preferably selected from the group of Fe, Co, Ni, Cu, Ag, Au, Ru, Rh, Pd, Os, Ir. Very particularly prefened metals are Cu, Pd, Ru, Rh. Ir and R. Examples of organic syntheses are, as well as asymmetric hydrogenations of prochiral unsaturated organic compounds, amine couplings, enantioselective ring openings and hydrosilylatlons. Particularly preferred metals are ruthenium, rtiodium and iridium. Depending on the oxidation number and coordination number of tfie metal atom, the metal connplexes may contain further ligands and/or anions. The metal complexes may also be cationic metal complexes. Such analogous metal complexes and their preparation have been described many times in the literature. The metal complexes may, for example, correspond to the general formulae XIV and XV AiMeU (XIV). (AiMeLnf">(E-)^ (XV). in which Ai is a compound of the formula I, L are identical or different monodentate, anionic or nonionic ligands, or two L are identical or different bidentate, anionic or nonionic ligands; n is 2,3 or 4 when L is a monodentate ligand, or n is 1 or 2 when L is a bidentate ligand; zis 1, 2 or 3; Me is a metal selected from the group Rh, Ir and Ru; where the metal has the oxidation states 0,1, 2, 3 or 4; E' is the anion of an oxygen acid or complex acid; and the anionic ligands balance the charge of the 1, 2, 3 or 4 oxidation states of the metal. For the compounds of the formula I, the above-described preferences and embodiments apply. Monodentate nonionic ligands may, for example, be selected from the group of the olefins (for example ethylene, propylene), allyls (ally!, 2-methallyl). solvating solvents (nitriles, linear or cyclic ethers, optionally n-alkylated amides and lactams, amines, phosphines, alcohols, carboxylic esters, sulphonic esters), nitrogen monoxide and carbon monoxide. Monodentate anionic ligands may, for example, be selected from the group of halide (F, CI, Br, I), pseudohalide (cyanide, cyanate, Isocyanate) and anions of carboxylic acids, sulphonic acids and phosphonic acids (carbonate, formate, acetate, propionate, methylsulphonate, trifluoromethylsulphonate, phenylsulphonate, tosylate). Bidentate nonionic ligands may, for example, be selected from the group of the linear or cyclic diolefins (for example hexadiene, cyclooctadiene, norbornadiene), dinitriles (malononitrile), optionally N-alkylated carboxamides, diamines, diphosphines, diols, acetonylacetonates, dicarboxyllc esters and disulphonic esters. Bidentate anionic ligands may, for example, be selected from the group of the anions of dicarboxyllc acids, disulphonic acids and diphosphonic acids (for example of oxalic acid, malonic acid, succinic acid, maleic acid, methylenedisulphonic acid and methylenedlphosphonic acid). Preferred metal complexes are also those in which E is -CI'. -Br, -I", CIO4'. CF3SO3', CH3SO3, HSO4". (CF3S02)2N-. (CF3S02)3C-. tetraarylborates, for example B(phenyl)4", B[bis(3,5-trifluoromethyl)phenyll4'. B[bls(3,5-dimethyl)phenyll4". B(C6F5)4" and B(4-methylphenyI)4. BF4", PFe". SbCle, AsFe" or SbFe". Especially preferred metal complexes which are suitable particularly for hydrogenations correspond to the formulae XVI and XVII [AiMezYZ] (XVI). [AiMezYJ^Er (XVII), in which Ai is a compound of the fonnula I; Me2 is rhodium or iridium; Y Is two olefins or one diene; Z is CI, Br or 1; and Er is the anion of an oxygen acid or complex acid. For the compounds of the formula I, the above-described embodiments and pre¬ferences apply. When Y Is defined as olefin, it may be C2-Ci2-olefins. preferably C2-C6-olefins and more preferably C2-C4-olefins. Examples are propene, but-1-ene and particularly ethylene. The diene may contain 5 to 12 and preferably 5 to 8 carbon atoms, and may be open-chain, cyclic or polycyclic dienes. The two olefin groups of the diene are preferably bonded by one or two CH2 groups. Examples are 1,3-pentadiene, cyclopentadiene, 1,5-hexadiene, 1,4-cyclohexadiene, 1,4- or 1,5-heptadiene, 1,4-or 1.5-cycloheptadiene, 1,4- or 1,5-octadiene. 1.4- or 1,5-cyclooctadiene and norbomadiene. Y is preferably two ethylene, or 1,5-hexadiene, 1,5-cyclooctadiene or norbomadiene. In formula XVI. Z is preferably CI or Br. Examples of Ei are BF4", CI04'. CF3SO3'. CH3SO3", HSO4". B(phenyl)4", B[bis(3.5-trifluoromethyl)phenyll4". PFg", SbCle", AsFe' or SbFe. The inventive metal complexes are prepared by methods known in the literature (see also US-A-5.371.256, US-A-5.446.844, US-A-6,683,241 and E. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehensive Asymmetric Catalysis I to III, Springer Verlag, Berlin, 1999, and literature cited therein). The inventive metal complexes are homogeneous catalysts or catalyst precursors which are activable under the reaction conditions and can be used for asymmetric addition reactions to prochiral unsaturated organic compounds; see E. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehensive Asymmetric Catalysis I to III, Springer Verlag, Beriin, 1999, and B. Cornils et al., In Applied Homogeneous Catalysis with Organometallic Compounds, Volume 1, Second Edition, Wiley VCH- Veriag, (2002). Further applications are, for example, the amination of aromatlcs or heteroaromatics which contain leaving groups, for example halide or sulphonate, with primary or secondary amines with palladium complexes, or the preferably Rh- catalysed enantioselective ring-opening reaction of oxabicyclic alkanes (M. Lautens et al. in Acc. Chem. Res. Volume 36 (203), pages 48-58). The metal complexes may, for example, be used for the asymmetric hydrogenatlon (addition of hydrogen) of prochiral compounds with carbon/cariDon or carbon/hetero- atom double bonds. Such hydrogenations with soluble homogeneous metal complexes are described, for example. In Pure and Appl. Chem,, Vol. 68, No. 1, pages 131-138 (1996). Preferred unsaturated compounds to be hydrogenated contain the C=C, C=N and/or C=0 groups. For the hydrogenation, preference Is given in accordance with the invention to using metal complexes of ruthenium, rhodium and iridium. The invention further provides for the use of the inventive metal complexes as homogeneous catalysts for preparing chiral organic compounds by asymmetric addition of hydrogen to a carbon or carijon-heteroatom double bond in prochiral organic compounds. A further aspect of the invention is a process for preparing chiral organic compounds by asymmetric addition of hydrogen to a carbon or carbon-heteroatom double bond In prochiral oiganic compounds in the presence of a catalyst, which is characterized in that the addition is perfonned in the presence of catalytic amounts of at least one inventive metal complex. Preferred prochiral unsaturated compounds to be hydrogenated may contain one or more identical or different C=C, C=N and/or C=0 groups in open-chain or cyclic organic compounds, where the C=C, C=N and/or C=0 groups may be part of a ring system or be exocyclic groups. The prochiral unsaturated compounds may be alkenes, cycloalkenes, heterocycloalkenes, and also open-chain or cyclic ketones, a.p-diketones, a- or p-ketocarboxylic acids and their a,p-ketoacetals or -ketals, estei^ and amides, ketlmines and kethydrazones. Alkenes, cycloalkenes, heterocyclo¬alkenes also include enamides. The process according to the invention can be performed at low or elevated temperatures, for example temperatures of -20 to ISO'C, preferably of -10 to 100°C, and more preferably of 10 to 80°C. The optical yields are generally better at relatively low temperature than at relatively high temperatures. The process according to the invention can be performed at standard pressure or elevated pressure. The pressure may, for example, be 10® to 2x10' Pa (pascal). Hydrogenatlons may be perfomied at standard pressure or at elevated pressure. Catalysts are used preferably In amounts of 0.00001 to 10 mol%, more preferably 0.00001 to 6 mol% and especially preferably 0.00001 to 2 mol%, based on the compound to be hydrogenated. The preparation of the ligands and catalysts and the hydrogenation can be performed without or in the presence of an inert solvent, in which case one solvent or mixtures of solvents may be used. Suitable solvents are, for example, aliphatic, cycloaliphatic and aromatic hydrocarbons (pentane, hexane, petroleum ether, cyclohexane. methylcyclohexane, benzene, toluene, xylene), aliphatic halohydrocarbons (methylene chloride, chloroform, di- and tetrachloroethane), nitriles (acetonitrile, propionitrile, benzonitrile), ethers (diethyl ether, dibutyl ether, t-butyl methyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydroHiran, dioxane, diethylene glycol monomethyl or monoethyl ether), ketones (acetone, methyl isobutyl ketone), carboxylic esters and lactones (ethyl acetate or methyl acetate, valerolactone), N-substituted lactams (N-methyl- pyrrolidone), carboxamides (dimethylacetamide, dimethylformamide), acyclic ureas (dimethylimidazoline), and sulphoxides and sulphones (dimethyl sulphoxide, dimethyl sulphone, tetramethylene sulphoxide, tetramethylene sulphone) and optionally fluorinated alcohols (methanol, ethanol, propanol, butanol, ethylene glycol mono- methyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, 1,1,1-trifluoroethanol) and water. Suitable solvents are also low molecular weight carboxylic acids, for example acetic acid. The reactions can be performed in the presence of cocatalysts, for example quaternary ammonium halides (tetrabutylammonium chloride, bromide or iodide) or protic acids, for example mineral acids such as HCI or strong organic acids such as trifluoroacetic acid, or mixtures of such halides and acids (see, for example, US-A- 5,371,256, US-A-5,446,844 and US-A-5,583,241 and EP-A-0 691 949). The presence of fluorinated alcohols, for example 1,1,1-trifluoroethanol, can also promote the catalytic reaction. The addition of bases, for example tertiary amines or phosphines, alkali metal hydroxides, secondary amides, alkoxides, carbonates and hydrogencarbonates may also be advantageous. The selection of a cocatalyst is guided mainly by the metal in the metal complex and the substrate. In the hydro- genation of prochiral arylketimines, the use of iridium complexes in combination with tetra-Ci-C4-alkylammonium iodides and mineral acids, preferably HI, has been found to be useful. The metal complexes used as catalysts may be added as separately prepared isolated compounds, or else formed in situ before the reaction and then mixed with the substrate to be hydrogenated. It may be advantageous to additionally add ligands in the reaction using isolated nfietal complexes, or to use an excess of the ligands in the in situ preparation. The excess may, for example, be 1 to 6 mol and preferably 1 to 2 mol, based on the metal compound used for the preparation. The process according to the invention is generally perfonned in such a way that the catalyst is initially charged and then the substrate, optionally reaction assistant and the compound to be added on are added, and then the reaction is started. Gaseous compounds to be added on, for example hydrogen, are preferably injected under pressure. The process can be performed continuously or batchwise in various reactor types. The chiral organic compounds preparable in accordance with the invention are active substances or intermediates for preparing such substances, especially in the sector of the preparation of aromas and flavourings, pharmaceuticals and agrochemicals. The examples which follow illustrate the invention. All reactions are performed with the exclusion of air under arigon and with degassed solvents. A) Preparation of liaands Examole A1: Preparation of ligand LI -PW)^ -P(CeH5)2 1 The synthesis of compound 11s described in the literature: P. Barbaro et al., Tetrahedron Letter 44 (2003) 8279-8283. Fe 1.93 ml (3.1 mmol) of 1.6 molar solution of n-butyl-LI (n-Bu-Li) In hexane are slowly added dropwise at -25°C to a solution of 1.42 g (3 mmol) of compound 1 in 10 ml of diethyl ether (DEE). After stining at -25°C for 30 minutes, the reaction mixture is cooled to -78°C, and a solution of 3.3 mmol of dichloro-t-butylphosphine in 20 ml of DEE is added slowly. After stirring at -78°C for 10 minutes, the cooling bath is removed and the mixture is allowed to rise to room temperature ovemight. The reaction mixture is subsequently admixed with 30 ml of degassed water and extracted with DEE. The organic phases are collected, dried over sodium sulphate and concentrated to dryness under reduced pressure on a rotary evaporator. The crude product is purified by chromatography (silica gel 60, eluent = ethyl acetate [EA]). The ligand L1 is obtained as a pure diastereomer and as a yellow solid in a yield of 81%. ^^P NMR (acetoneds, 161.97 MHz): 8 32.6 (s), 4.8 (s). ^H NMR (CeDg, 300 MHz) characteristic signals: 7.61-7.01 (m. 10H), 6.20 (d, ^JPH= 460 Hz, PH). 4.48 (s. 2H), 4.37 (s, 5H), 4.24 (s, 1H), 3.88-3.74 (m. 1H). 1.51 (m, 3H), 1.13 (d, 9H). Example A2: Preparation of ligand L2 pi:' P(C6Hs)2 Fe 0 The procedure is analogous to Example A1, except that dichlorophenylphosphlne Is used in place of dichloro-t-butylphosphine. The ligand L2 is obtained as a pure diastereomer and as a yellow solid in a yield of 61%. NMR (CDCI3,161.97 MHz): 6 14.6 (s), 6.4 (s). ^H NMR (CeDe, 300 MHz) characteristic signals: 7.74-6.93 (m, 15H). 6.37 (d, ^JpH= 495 Hz, PH), 4.44 (s, 1H), 4.30 (s, IH), 4.27 (s, 5H). 4.08-3.98 (m, 1H), 3.53 (s, 1H), 1.53 (m, 3H). Example A3: Preparation of ligand L3 NCCHj), N(CH3)2 The synthesis of compound 2 is described in WO 96/16971. a) Preparation of compound 3 12.1 ml (15.7 mmol) of a 1.3 molar secondary butyl-Li (s-BuLi) solution in cydo- hexane are slowly added dropwise with ice cooling and stining to 5.0 g (13 mmol) of compound 2 (S.S' configuration) in 30 ml of tert-butyl methyl ether (TBME) at such a rate that the temperature of the reaction mixture does not exceed 2°C. The reaction mixture is stinred further at 0°C over 1.5 hours, then 5.3 g (15.7 mmol) of bis(3.5- dimethyl-4-methoxyphenyl)phosphine chloride are added dropwise to the red-orange suspension within 15 minutes. After further stirring at 0°C for one hour, the cooling is removed. The reaction mixture is allowed to wann slowly to room temperature and stirred for another 1 hour, and then admixed with 10 ml of water. The mixture is extracted first vwth EA and then with TBME. The organic phases are combined and dried over sodium sulphate, and the solvent is distilled off completely under reduced pressure in a rotary evaporator. The crude product is purified by chromatography (silica gel 60, eluent = 2:1 heptane/EA with 2% triethylamine). The pure compound 3 is obtained as a yellow solid with a yield of 67%. NMR (CeDe, 121 MHz): 5 -23.5 (s). ^H NMR (CeDe, 300 MHz) characteristic signals: 5 7.60 (d, 2H), 7.14 (d, 2H). 4.37 (m, 1H), 4.24 (m, 1H). 4.19 (m, 1H). 4.14 (m, IH), 4.02 (m, 2H), 3.86 (m, 2H), 3.39 (s, 3H), 3.30 (8, IH), 2.78 (q, IH), 2.17 (s, 6H), 2.12 (s, 6H), 2.02 (s, 6H). 1.94 (s, 6H), 1.20 (m, 6H). b) Preparation of ligand L3 2.4 ml of a 1.3 molar solution of s-BuLi in cyclohexane are added dropwise at -20°C with stining to a solution of 1.6 g (2.5 mmol) of compound 3 in 20 ml of TBME, and the reaction mixture is subsequently stirred further at this temperature for another 1.5 hours. The red-orange solution is then cooled to -78°C, and a solution of 0.8 g (5 mmol) of t-butyldichlorophosphine is slowly added dropwise. The mixture is stinred at -78°C for another one hour, then the cooling bath is removed and the mixture is allowed to wann to room temperature ovemight. The reaction mixture is admixed with 10 ml of water, neutralized with a saturated NaHCOa solution and extracted with TBME. The organic phases are collected and dried over sodium sulphate, and the solvent is distilled off completely under reduced pressure on a rotary evaporator. The solid orange crude product (1.9 g) is purified by chromatography (silica gel 60, eluent = 1:1 heptane/EA with 1% triethylamine). The pure compound L3 Is obtained as a yellow solid with a yield of NMR (CeDe, 121 MHz): S +35.6 (s). -24.8 (s). ^H NMR (CeDe, 300 MHz) characteristic signals: 5 7.67 (d, 2H), 7.21 (d, 2H), 7.12 (d, ^JPH= 465 Hz, 1H), 5.21 (m, 1H), 4.79 (m, 1H), 4.39 (m, 1H), 4.34 (m, 1H), 4.30 (m. 1H), 4.31-4.09 (m, 2H), 3.63 (m. 1H), 3.41 (s, 3H), 3.32 (s. 3H), 2.22 (s. 6H), 2.12 (s, 6H), 2.01 (s, 6H), 1.94 (s, 6H). 1.30 (d, 3H), 1.21 (d, 3H), 0.99 (d, 9H). Example A4: Preparation of ligands L4 and L5 ^^NCCHa)^ Oo 0 4 a) Preparation of compound 4 12.9 ml (75.9 mmol, 3.0 equivalents) of 2,2,6,6-tetramethylpiperidine are dissolved in 100 ml of absolute tetrahydrofuran (THF) and cooled to 0°C. 45.8 ml (73.4 mmol, 2.9 equivalents) of n-Bu-Li solution (1.6 m in hexane) are added dropwise. Sub¬sequently, the mixture is stirred at 0°C for one hour (solution A). 8.50 g (25.3 mmol, 1.0 equivalent) of compound 1 are dissolved in 70 ml of absolute THF and cooled to -70°C (solution B). Solution A Is added dropwise to solution B with stining over 30 minutes, in the course of which it is ensured that the temperature does not exceed -30°C. The mixture is then stirred further over 1.5 hours, in the course of which the temperature is kept at -35°C. Thereafter, the reaction mixture is cooled to -78°C. and 6.1 ml (32.9 mmol, 1.3 equi¬valents) of diphenylphosphine chloride are added. The temperature is allowed to rise slowly to -25'C with stirring within 1.5 hours. The reaction mixture Is then admixed with 100 ml of water. The mixture is extracted with TBME. The combined organic phases are dried over sodium sulphate and freed of the solvent on a rotary evaporator. The resulting brown oil Is purified chromatographically (silica gel 60. eluent = acetone). The chromatographed product is obtained In virtually quantitative yield. Recrystallization in methanol gives rise to the compound 4 as a yellow-orange solid in a yield of 73%. ^^P NMR (CeDe, 121 MHz): 8 -18.2 (s). ^H NMR (CeDe, 300 MHz) characteristic signals: 5 7.66 - 6.90 (10 aromatic H). 4.03 (s, 5H). 3.96 (m, 1H), 3.90 (q, 1H). 2.18 (s. 6H). 1.31 (d. 3H). b) Preparation of the diastereomeric ligands L4 and L6 1.5 ml of a 1.6 molar solution of n-Bu-LI in hexane are added dropwise at O'C witii stirring to a solution of 1.0 g (1.9 mmol) of compound 4 in 20 ml of TBME, and the reaction mixture is subsequently stirred further at this temperature for another 2 hours. The red-orange solution Is then cooled to -78°C, and a solution of 0.6 g (3.8 mmol) of t-butyldichlorophosphine is slowly added dropwise. The mixture is stinred at -78°C for another one hour. The cooling bath is then removed and the temperature is allowed to rise to room temperature overnight. The reaction mixture is admixed with 10 ml of water, neutralized with unsaturated NaHCOs solution and extracted with TBME. The organic phases are collected and dried over sodium sulphate, and the solvent is distilled off completely under reduced pressure on a rotary evaporator. The resulting solid orange crude product (1.2 g) contains two diastereomers. These are separated by chromatography (silica gel 60. eluent = 2:1 heptane/EA with 1% triethylamine). The first fraction affords 266 mg of tfie first diastereoisomer ligand L4 (yellow solid, 27% yield), and the second, larger fraction 560 mg of the second diastereomer L5 (yellow solid, 55% yield). Ligand L4: NMR (CD3OD. 121 MHz): 6 +47.8, -22.2. ^H NMR (CD3OD, 300 MHz) characteristic signals: 7.69 - 7.12 (various signals, 10 H), 7.0 (d, ^Jph= 470 Hz. 1H). 4.78 (m. 1H), 4.42 (m. 1H). 4.07 (s, 5H). 2.09 (s. 6H). 1.33 (d. 3H), 1.05 (d. 9H). Ligand L5: NMR (CD3OD, 121 MHz): 8 +48.5 (d), -24.9 (d). ^H NMR (CD3OD, 300 MHz) characteristic signals: 7.65 - 7.12 (various signals, 10 H), 7.73 (d of d, ^JPH= 472 Hz, IH), 4.83 (m, 1H), 4.30 (m, 1H), 4.05 (s, 5H), 2.12 (s, 6H), 1.29 (d, 3H). 1.03 (d, 9H). Example A5: Preparation of ligand L6 C(CH3)3 ...„p ^ L6 a) Preparation of cxjmpound 5 The preparation of compound 5 is described by M. Cereghetti et al. in Tetrahedron Letter 37 (1996) 5347-5350. b) Preparation of ligand L6 0.75 ml (1.2 mmol) of n-Bu-Li (1.6 M in hexane) is added dropwise at -78°C with stirring to a solution of 500 mg (1 mmol) of compound 5 in 15 ml of TBME. After stirring at -78'C for 1 hour, 320 mg (2 mmol) of t-butyldichlorophosphine are added. After 2 hours, the cooling is removed and the temperature is allowed to rise to room temperature overnight. The reaction mixture is admixed with 10 ml of water and extracted with TBME. The organic phases are collected, washed with aqueous NaHCOa solution and then with NaCI solution, and dried over sodium sulphate, and the solvent is distilled off completely on a rotary evaporator. The crude product contains the desired product as a mixture of 2 diasteromers in a ratio of about 5:2 (crude yield 77%). These can be separated by column chromatography (silica gel 60, eluent = first 1:2 EA/heptane, then 1:1 and finally only EA). The diastereomer obtained In a larger amount is referred to as ligand L6, which is eluted before the diasteromer present In a smaller amount (both are white solids). Ligand L6: NMR (CeDe, 121 MHz): 5 +36.5, -16.0. ^H NMR (CgDe, 300 MHz) characteristic signals: 5 8.02 - 6.88 (16 arom. H). 6.98 (d, ^Jph= 461 Hz, 1H). 1.81 (s, 3H). 1.36 (s. 3H). 0.96 (s, 9H). Example A6: Preparation of ligand L7 "2 ^ CH3 CH, " ^ ^^ H ^ L7 0. O 3 a) Preparation of compound 6 5.21 g of compound 1 (15.5 mmol) In 30 ml of acetic anhydride are heated to 135^0 with stirring over 4 hours. After cooling, the mixture is extracted with water/toluene. The organic phases are collected and dried over sodium sulphate, and the solvents are distilled off completely on a rotary evaporator under reduced pressure (20 ton-). The crude product is then purified by chromatography (silica gel 60, eluent = heptane). Compound 6 is obtained as a red-brown oil in a yield of 80%. ^H NMR (CeDe, 300 MHz) characteristic signals: 5 6.89 (m, 1H). 5.38 (m. 1H), 5.08 (m. 1H), 4.28 (m. 1H), 4.16 (m. 1H), 3.94 (s. 5H), 3.80 (m, 1H). b) Preparation of compound 7 A solution of 7.1 g (24,4 mmol) of compound 6 in 35 ml of THF is stirred intensively in the presence of 0.7 g of catalyst (5% Rh/C, Engelhard) in a hydrogen atmosphere (standard pressure) until no further hydrogen is consumed. The reaction mixture is then placed under argon and the catalyst is filtered off. After washing with a little THF, the filtrate is free fi"om the solvent completely on a rotary evaporator. Compound 8 is obtained in quantitative yield as an orange-brown oil. ^H NMR (CeOe, 300 MHz) characteristic signals: 8 4.24 (m, 1H). 3.96 (s, 5H), 3.77 (m, 1H). 3.71 (m, 1H), 2.42 - 2.23 (m. 2H), 1.05 (t, 3H). c) Preparation of compound 8 1.74 ml (10.2 mmol. 3.0 equivalents) of 2,2,6.6-tetramethylplperidine are dissolved in 20 ml of absolute THF and cooled to 0®C. 6,2 ml (9.9 mmol, 2.9 equivalents) of n-Bu-Li solution (1.6 m In hexane) are added dropwise. Subsequently, the mixture Is stirred at 0°C for one hour (solution A). 1.0 g (3.41 mmol, 1.0 equivalent) of compound 7 are dissolved In 10 ml of absolute THF and cooled to -70'C (solution B). Solution A is added dropwise to solution B over 30 minutes, in the course of which it is ensured that the temperature does not exceed -30'C. The mixture Is then stirred over 4 hours, in the course of which the temperature is kept between -40'C and -30°C. The reaction mixture is cooled to -78°C, and 0.82 ml (4.44 mmol, 1.3 equi¬valents) of diphenylphosphine chloride is added. The temperature Is allowed to rise slowly to -25°C with stlning within 1.5 hours. The reaction mixture is then admixed with 20 ml of water. After adding a little saturated ammonium chloride solution, the mixture is extracted with DEE and methylene chloride. The combined organic phases are dried over sodium sulphate and freed of the solvent on a rotary evaporator. The resulting brown oil is purified chromatographically (silica gel 60, eluent = first 20:1 heptane-EA, then 10:1 heptane-EA). Compound 8 is obtained as a brown solid with a yield of 62%. NMR (CgDe, 121 MHz): 8 -18.2 (s). ^H NMR (CeDe, 300 MHz) characteristic signals: 8 7.62 (m. 2H), 7.38 (m, 2H), 7.1 - 6.9 (m, 6H), 3.99 (s, 5H), 3.94 (m, 1H). 3.59 (m, 1H). 2.47 - 2.26 (m, 2H), 1.07 (t, 3H). d) Preparation of ligand L7 0.31 ml (0.60 mmol) of a 1.6 molar solution of n-Bu-Li In hexane are slowly added dropwise at -30°C to a solution of 200 mg (0.419 mmol) of compound 8 in 10 ml of TBME. After stining at -SO^C for 1 hour, the reaction mixture is cooled to -78°C, and 0.11 ml (0.84 mmol) of dichlorophenylphosphine is added slowly. After stinging at -78°C for 20 minutes, the cooling bath is removed and the mixture Is allowed to wami to room temperature overnight. The reaction mixture Is subsequently admixed with 10 ml of degassed water, the pH Is adjusted to 7-8 with saturated aqueous NaHCOa solution, and then the mixture is extracted with EA. The organic phases are collected, dried over sodium sulphate and concentrated to dryness under reduced pressure on a rotary evaporator. The crude product is purified by chromatography (silica gel 60, eluent = increasingly polar: first 1:3 EA/heptane, then 1:1 and finally pure EA). The ligand L7 Is obtained as a pure diastereomer and as a yellow solid in a yield of 45%. NMR (CeDe, 121 MHz): 8 +13.4 (d), -24.0 (d). ^H NMR (CeDe, 300 MHz) characteristic signals: 8 8.82 and 7.73 (d of d, ^Jph= 489 Hz. 1H), 7.60 - 6.80 (15 aro¬matic H), 4.31 (s, 5H). 4.22 (m, 1H), 3.94 (m. 1H). 2.84 (m, 2H), 0.97 (t, 3H). Example A7 and A8: Preparation of ligands L8 and L9 CH3 9M3 CH3 10 ^^ L8 ^ -I' - Compound 9 (1-[(dimethylamino)eth-1-yl]-2-bromofenrooene) is prepared as described in the literature: J.W. Han et al.. Helv. Chim. Acta, 85 (2002) 3848-3854. a) Preparation of compound 10 10 g (29.8 mmol) of compound 9 and 7.22 ml (35.7 mmol) of dicyclohexylphosphine are stirred in 40 ml of acetic acid at 85°C over 15 hours and then at 100°C for 5 hours. After cooling, the red-brown solution is extracted with water and toluene, and then with saturated aqueous sodium chloride solution and toluene. The organic phase is dried over sodium sulphate, and the solvent is distilled off on a rotary evaporator. After chromatographic purification using a short column (150 g of silica gel 60; eluent = ethyl acetate EA), the desired red-brown product 10 is obtained in a yield of 95%. NMR (CeDe, 121 MHz): 5 +22.5 (s). 'H NMR (CeDe, 300 MHz): 84.29 (m, 1H), 4.02 (s. 5H). 3.89 (m, IH), 3.76 (m, 1H), 3.105 (q, 1H), 1,57 (d of d, 3H), 2.0-1.0 (m, 22H). b) Preparation of compound L8: PeH,,)^ 4.3 ml (6.77 mmol) of n-BuLi (1.6 M in hexane) are added dropwise at 0°C to a suspension of 3.01 g (6.15 mmol) of compound 10 in 30 ml of diethyl ether. The resulting red-brown solution is stin-ed further at O'C for 30 min before it is cooled to -70'C. 0.92 ml (6.7 mmol) of P,P-dichlorophenylphosphine are then added. The cooling is removed and the resulting light brown-orange suspension is stin-ed at room temperature for 2 hours. The reaction mixture is then hydrolysed with 20 ml of water and then extracted with water and methylene chloride. The organic phase is dried over sodium sulphate and the solvent is distilled off on a rotary evaporator. The crude product can be purified by chromatography (silica gel 60; eluent =1:1 EA/heptane in the presence of 0.4% triethylamine). The desired product L8 is obtained as a firm light brown solid (yield 40%). NMR (CEDE, 121 MHz): 8 +14.99 (d. JPP= 30 Hz). +13.95 (d. Jpp= 30 Hz). ^H NMR (CeDe, 300 MHz): 5 9.45 and 7.82 (two d, 1H), 7.75- 7.68 (m, 2H). 7.15-7.02 (m. 3H), 4.29 (s, 5H), 4.14 (s, 1H), 3.93 (q, 1H), 3.87 (m, 1H), 3.59 (m. 1H). 1.52 (d of d, 3H), 2.0 -1.0 (m, 22H). c) Preparation of compound L9: 4.3 ml (6.77 mmol) of n-BuLi (1.6 M in hexane) are added dropwise at 0°C to a suspension of 3.0 g (6.13 mmol) of compound 10 in 15 ml of diethyl ether. The resulting red-brown solution is stin-ed further at 0°C for 30 min before it is cooled to -70X. A solution of 1.07 g (6.7 mmol) of P,P-dichloro-tert-butylphosphine in 5 ml of diethyl ether (DEE) is then added. The cooling is removed and the resulting thick orange-red suspension Is stirred at room temperature for 2 hours. The reaction mixture is then hydrolysed with 20 ml of water, and subsequently extracted with water, saturated aqueous sodium chloride solution and methylene chloride. The organic phase is dried with sodium sulphate, and the solvent is distilled off on a rotary evaporator. The crude product can be purified by chromatography (silica gel 60; eluent = EA with 0.4% triethylamine). The desired product L9 is obtained as a solid yellow-orange-brown solid (yield 64%). NMR (CeDe, 121 MHz): 8 +34.99 (d, Jpp= 28 Hz), +12.81 (d, Jpp= 28 Hz). ^H NMR (CeDe. 300 MHz) characteristic signals: 8 8.34 and 6.82 (two d, 1H), 4.40 (s, 5H), 4.28 (m, 1H), 4.08 (m, 1H), 4.03 (m, 1H), 3.48 (q of d, 1H), 1.47 (d of d, 3H), 1.24 and 1.18 (s, 9H), 2.0 - 1.0 (m, 22H). Example A9: Preparation of ligand L10 CH3 CH3 CH3 V Br ^^ . o L10 o. o. a) Preparation of compound 11 5 g (14.9 mmol) of compound 9 In 23.8 g of a 10% solution of di-tert-butylphosphine in acetic acid are stin-ed at 105°C over 7.5 hours. After cooling, the red-brown solution is extracted with water and toluene and then with saturated aqueous sodium chloride solution and methylene chloride. The organic phases are dried over sodium sulphate, and the solvent is distilled off on a rotary evaporator. After chromatographic purification using a short column (150 g of silica gel 60; eluent = EA with 1% triethylamine), the desired red-brown product 11 is obtained in a yield of 70%. ^^P NMR (CeDe. 121 MHz): 5 +47.23 (s). ^H NMR (CeDe, 300 MHz) characteristic signals: 4.31 (m. 1H). 3.99 (s, 5H), 3.83 (m, 1H), 3.70 (m. 1H). 3.19 (q. 1H). 1.73 (d of d. 3H), 1.34 (d. 9H). 1.15 (d. 9H). b) Preparation of compound L10: 3.2 ml (5.11 mmol) of n-BuLi (1.6 M in hexane) are added dropwise at 0°C to a solution of 2.03 g (4.64 mmol) of compound 11 in 20 ml of diethyl ether (DEE). The resulting red-orange suspension is stin-ed further at 0°C for 1.5 hours before it Is cooled to -70°C. A solution of 0.81 g (6.7 mmol) of P.P-dichloro-tert-butylphosphine in 5 ml of DEE is then added. The cooling is removed and the resulting orange suspension is stirred at room temperature for 2 hours. The reaction mixture is then hydrolysed by adding 20 mi of water, and subsequently extracted with 0.05N NaOH and methylene chloride. The organic phase is dried over sodium sulphate and the solvent is distilled off on a rotary evaporator. The crude product can be purified by chromatography (silica gel 60; eluent = EA with 0.4% triethylamine). The desired product L10 is obtained as a red-orange, almost solid oil (yield 85%).®^P NMR (CeDe, 121 MHz): 5 +44.83 (d, JPP= 39 Hz), +35.01 (d, JPP= 39 Hz). ^H NMR (CeDe, 300 MHz) characteristic signals: 6 8.51 and 6,96 (two d, 1H), 4.35 (s, 5H), 4.19 (m, 1H), 4.14 (m, 1H), 3.80 (q. 1H), 3.99 (m. 1H), 1.75 (d of d, 3H). 1.36 and 1.32 (two s, 9H). 1.22 and 1,16 (two s, 9H), 1.12 and 1.09 (two s, 9H). Example A10: Preparation of ligand L11 \ 9H3Q Oi 13 12 —N-;^ jr Fe L11 15 o a) Preparation of 1-dicyclohexylphosphino-1'-bromoferrocene of ttie formula 13: 120 ml (0.3 mol) of n-BuLi (2.5 M in hexane) are added dropwise at a temperature of b) Preparation of compound 16 (reaction solution 1): 4.0 ml (5.2 mmol) of s-BuLi (1.3 M in cyclohexanone) are added dropwise at -JS^C with stirring to a solution of 1.29 g (5 mmol) of compound 15 in 5 ml of TBME. The temperature is then allowed to rise to room temperature and the mixture is stirred further for 1.5 h. The resulting suspension is then injected with elevated pressure (argon) through a cannula into a second vessel in which a solution of 0.44 ml (5 mmol) of PCI3 in 10 ml of TBME is stin-ed at -78X. After the addition, the temperature Is allowed to rise to OX, and the resulting suspension is stinred further for another 1.5 hours. After adding 10 ml of THF, reaction solution 1 comprising compound 16 is obtained. c) Preparation of compound L11: 3.25 ml (5.2 mmol) of n-BuLi (1.6 molar in hexane) are added dropwise at -78°C with stirring to a solution of 2.31 g (5 mmol) of compound 13 in 10 ml of TBME. The temperature is then allowed to rise to O^C and stirred further for 40 minutes. A red reaction solution comprising the llthiated compound 14 is obtained. This is added dropwise at O'C with stirring to the reaction solution 1 comprising compound 16. On completion of addition, the cooling is removed and the resulting suspension is stirred overnight. The reaction mixture is hydrolysed with 50 ml of water and 20 ml of saturated aqueous sodium bicarbonate solution, and extracted with methylene chloride. The organic phase is dried over sodium sulphate and the solvent Is distilled off on a rotary evaporator. After chromatographic purification (silica gel 60; eluent = 2:1 to 1:2 THF/methanol), the desired product L11 is obtained as an orange solid. NMR (CeDe. 121 MHz): 8 +13.59 (s), -7.81 (s). ^H NMR (CeDe. 300 MHz) characteristic signals: 5 9.04 and 7.39 (two s, 1H), 4.84 (m. 1H), 4.66-4.62 (m, 2H). 4.54 (q, 1H), 4.44 (m. 1H). 4.38 (m. 1H), 4.32 (m, 1H). 4.25 (s. 5H). 4.28-4.21 (m. 2H). 4.13 (m. 1H), 3.96 (m. 1H), 3.92 (m. 1H), 2.19 (s, 6H). 1.12 (d, 3H). 2.1-1.0 (m, 22H). B) Preparation of metal complexes Example B1: Preparation of an Ir complex (COD = cyclooctadiene) A solution of 50.2 mg (0.1 mmol) of ligand LI in 2 ml of methanol is added to a solution of 127.2 mg (0.1 mmol) of [lr(C0D)2]BArF in 2 ml of methanol, and the reaction mixture is stirred over 30 minutes. The methanol is removed under reduced pressure and the brown-red residue is washed with pentane. NMR (161.97 MHz, 300 K, CD2CI2): 8 = 103.1 (d, Jpp = 23.8): 23.4 (d, Jpp = 23.8). Example B2: Preparation of an Ru complex A solution of 50.2 mg (0.1 mmol) of ligand LI in 2 ml of methanol is added to a solution of 30.6 mg (0.05 mmol) of [RuCl2(p-methylcumene)]2 in 2 ml of methanol. and the reaction mixture is stin"ed over 30 minutes. The methanol is removed under reduced pressure and the residue is washed with pentane. NMR (161.97 MHz, 300 K, MeOH-d4): 6 = 66.4 (s), 25.9 (s). Example B3: Preparation of an Rh complex A solution of 50.2 mg (0.1 mmol) of ligand LI in 2 ml of methanol is added to a solution of 30.6 mg (0.05 mmol) of [Rh(C0D)2]BArF in 2 ml of methanol, and the reaction mixture is stirred over 30 minutes. The methanol is removed under reduced pressure and the residue is washed with pentane. NMR (161.97 MHz, 300 K, CDCI3): 6 = 62.4 (s). 33.4 (d, ^JPRH = 153 Hz), 23.5 (d, ^JPP = 23 Hz). C) Use examples All operations are performed under argon and with degassed solvents. Example C1: 4.73 mg (0.0127 mmol) of [Rh(norbornadiene)2]BF4 and 6.67 mg (0.0133 mmol) of ligand L1 (ratio of ligand to metal = 1.05) are stirred In 2 ml of methanol over 10 minutes. A solution of 400 mg (2.5 mmol) of dimethyl itaconate (DMI) in 4 ml of methanol and then sufficient methanol (4 ml) that the substrate concentration is 0.25 M are added to this solution. The argon is drawn off with vacuum and the vessel is connected to a hydrogen supply (1 bar). Switching on the stirrer starts the hydrogenation. After 1 hour, the stirrer is switched off and the solution is placed under argon again. Conversion and enantiomeric excess (ee) are detemriined by gas chromatography with the aid of a chiral column (Lipodex E): the conversion is complete and the ee is 87%. Examples C2-C32: The hydrogenations of further substrates, which are compiled in Table 1 below are performed in an analogous manner. The hydrogenations with higher hydrogen pressure are performed in a steel autoclave. In these, the reaction solutions are injected into the argon-purged autoclave with a cannula under an argon countercurrent. The results are reported in Table 2 below. The abbreviations in Table 1 mean: ee = enantiomeric excess. GC = gas chromatography. TMS = trimethylsilyl. HPLC = high-pressure liquid chromatography. Table 1: Substrates Substrate Structures Determination of conversion and ee DMI si^COOMe ^COOMe Hj t^XOOMe COOMe GC with chlral column: Lipodex-E MAA ^CCXX>l3 NHCOCH, Ha vyCOOCH, NHCOCH, GC with chiral column: Chirasil-L-val MAC crc: H2 ^sss^v'V^COOMe NHCOCH, GC with chiral column: Chirasil-L-val ACA l!^ NHCOCH, H, NHCOCH, First derivatization with TMS-diazomethane, then GC with chiral column: Chirasil-L-val MCA Hj First derivatization with TMS-diazomethane, then HPLC with chiral column: Chiracel-OB Z-EAAC Ha ■ GC with chiral column: Betadex-110 E-EAAC Ha GC with chiral column: Betadex-110 MEA Ha HPLC with chiral column: Chiracel-OD-H EOP Ha GC with chiral column: Lipodex-E EBAC Ha HPLC with chiral column: Chiracel-OD-H MPG Ha - HPLC with chiral column: Chiracel-OD-J KEPL H, ■ GC with chiral column: Lipodex-E Table 2: Hydrogenation results No. Lig. Metal Substrate [S] S/C Sol. P T t [hi 0 (%) ee (%) C1 L1 DM! 0.25 200 MeOH 1 25 1 100 87 C2 L1 DMI 0.36 100 THF 1 25 14 100 96.7 C3 L1 MAA 0.25 200 MeOH 1 25 1 100 48 C4^> L1 Ru®> EOF 0.51 1000 EtOH 80 80 16 100 91 C5 LI Ru®) EBAC 0.51 1000 EtOH 80 80 20 100 88 C6 L1 Rh^) E-EAAC 0.25 100 EtOH 1 25 21 100 95.6 C7 L1 Rh^) E-EAAC 0.63 500 EtOH 5 25 20 100 95.6 C8 L1 Rh") ACA 0.1 25 DCE 1 25 1 100 98.6 C9 L1 Rh"^) KEPL 0.1 25 toluene 20 25 14 100 88.8 C10 L2 Rh^> DMI 0.25 200 MeOH 1 25 1 100 99.4 L2 Ir^) MEA* 0.25 200 toluene 80 25 21 100 43 C12 L3 Rh^> MCA 0.25 200 MeOH 5 25 40 91 19 C13 L3 Rh") MPG 0.25 200 toluene 80 25 23 100 21 L4 Ru®> EOF 0.25 200 EtOH 80 80 21 7 68 C15 L4 Rh®) MAA 0.25 200 MeOH 1 25 1 100 98.8 C16 L4 Rh®) DMI 0.25 200 MeOH 1 25 2 100 82.7 L5 Ru®> EOF 0.25 200 EtOH 80 80 21 30 46 L6 Ru®^ EOF 0.25 200 EtOH 80 80 21 100 10 C19 L6 Rh«) MAA 0.25 200 MeOH 1 25 1 100 99 C20 L6 Rh®) DMI 0.25 200 MeOH 1 25 2 100 94.9 C21 LB Rh*") MAC 0.36 100 DCE 1 25 2 100 97.0 L8 Rh^) ACA 0.36 100 DCE 1 25 2 100 88.7 C23 L8 Rh") MAA 0.36 100 DCE 1 25 2 100 98.8 C24 L8 Rh'^) ETFY 0.1 25 toluene 20 25 14 100 72.2 C25 L8 Rh'^) KEFL 0.1 25 toluene 20 25 14 100 83.3 C26®) L9 Ru^ KEFL 0.1 25 EtOH 20 25 14 100 83.3 C27 L9 Rh'^) KEPL 0.1 25 toluene 20 25 14 100 73.2 C28 L10 Rh") MAC 0.1 25 THF 1 25 2 100 92.1 C29 L10 Rh^> MAA 0.36 100 THF 1 25 2 100 94.3 C30®) L10 Rh') KEPL 0.1 25 toluene 20 25 14 100 87.0 C31 L11 Rh®) MAA 0.25 200 MeOH 1 25 1 100 83.2 C32 L11 DMI 0.25 200 MeOH 1 25 1 100 94.5 Additions: ^^ 1N HCI (1.2% based on solvent volume); ^^ 2 equivalents of tetrabutyl- ammonium iodide/lr and CF3COOH (0.6% based on solvent volume); HCI (0.6% based on solvent volume); equivalents if 1,4-diazobicyclo[2.2.2]octane/ln 4 equivalents of 1,4-dlazobicyclo[2.2.2]octane/lr In the table: [S] means molar substrate concentration; S/C means substrate/catalyst ratio; t means hydrogenation time; Lig. means ligand, Sol. means solvent (MeOH = methanol; EtOH = ethanol; Tol = toluene; THF = tetrahydrofuran; DCE = 1,2-dichloroethane); Metal means metal precursor which is used in the hydrogenations: Rh®^ = [Rh(norbomadiene)2]BF4; Rh"^ = [Rh(cyclooctadiene)Cll2; Rh'^ = [Rh(norbomadiene)triflate]2; [lr(cyclooctadiene)CI]2; Ru®^= [Rul2(p-methyl- cumene)]2; Ru^= [RuCl2(p-methylcumene)]2; Lig. = ligand, C = conversion; Conf. = configuration. Claims 1. Compounds of the formula I having at least two chiral centres in the form of mixtures of diastereomers or pure diastereomers secondary phosphine-Q-P*(=0)HRi (I), in which secondary phosphine is a secondary phosphine group with hydrocarbon radicals or heterohydrocarix)n radicals as substituents; Q is a bivalent bisaryl or bisheteroaryl radical with an axial chiral centre to which the two phosphorus atoms are bonded in the ortho positions to the bisaryl or bisheteroaryl bridge bond, or Q is a bivalent ferrocenyl radical with a planar chiral centre, or Q is a bivalent ferrocenyl radical without a planar chiral centre, to which the phosphorus atom of the secondary phosphine is bonded directly or via a C1-C4- carbon chain to a cyclopentadienyl ring, the -P*(=0)HRi group Is bonded either on the same cyclopentadienyl ring in ortho position to the bonded secondary phosphine or on the other cyclopentadienyl ring; P* is a chiral phosphorus atom, and Ri is a hydrocartDon radical, a heterohydrocarbon radical or a fen-ocenyl radical, where Ri is a ferrocenyl radical with a planar chiral centre when Q as a bivalent ferrocenyl radical does not have a planar chiral centre. 2. Compounds according to Claim 1, characterized in that Ri is a hydrocarbon radical selected from the group of linear or branched Ci-Cie-alkyI; unsubstltuted or Ci-Ce- alkyl- or Ci-Ce-alkoxy-substituted C5-Ci2-cycloalkyl or C5-Ci2-cycloalkyl-CH2-; phenyl, naphthyl, Hiryl or benzyl; or halogen-, Ci-Ce-alkyI-, trifluoromethyl-, Ci-Ce-alkoxy-, trifluoromethoxy-, (C6H5)3SI-, (Ci-Ci2-alkyl)3Si-, or secondary amino-substituted phenyl, naphthyl, furyl or benzyl, or Ri Is an unsubstituted or mono- or polysubstituted ferrocenyl radical. 3. Compounds according to Claim 1, characterized in that the secondary phosphine corresponds to the fonnula -PR2R3 in which R2 and Ra are each independently a hydrocarbon radical which has 1 to 18 carbon atoms and is unsubstituted or substituted by Ci-Ce-alkyI, trifluoromethyl. Ci-Ce-allcoxy. trifluoromethoxy, (C1-C4- alkyl)2annino, (C6H5)3Si. (Ci-Gi2-aikyi)3Si. halogen, and/or O heteroatoms. 4. Compounds according to Claim 1, characterized in that Q in formula I represents radicals in which two hydrocarbon aromatics, two heteroaromatics or one hydrocarbon aromatic and one heteroaromatic are joined to one another. 5. Compounds according to Claim 1, characterized in that they correspond to the fomnulae Ilia. Vila. Villa. IXa and XXa 1 NR (Ilia), (Vila). (Villa). (IXa). Horn, XXa. in which the 3.3' and/or 4,4' positions In formula Ilia may be substituted by Ci-C4-alkyl. C1-C4- alkoxy. trifluoromethyl or trimethylsilyl; Ri is CrCs-alkyl. unsubstituted cydopentyl or cyclohexyl or cydopentyl or cyclohexyl substituted by 1 to 3 CrC4-alkyl or Ci-C4-alkoxy, or benzyl and phenyl which are unsubstituted or substituted by 1 to 3 Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-fluoroalkyl or Ci-C4-fluoroalkoxy, F and CI; R2 and R3 are each independently a hydrocarbon radical which has 1 to 18 carbon atoms and is unsubstituted or substituted by Ci-Ce-alkyI, trifluoromethyl, Ci-Ce- alkoxy, trifluoromethoxy, (Ci-C4-alkyl)2amino, (C6H5)3Si, (Ci-Ci2-alkyl)3Si, halogen, and/or O heteroatoms; R4 is hydrogen or Independently as defined for R5; Rs^is Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-hydroxyalkyl. C2-C4-hydroxyalkoxy, C1-C4- alkoxy-Ci-Ca-alkyl, Ci-C4-alkoxy-Ci-C2-alkoxy, trifluoromethyl or trimethylsilyl, or R4 and R5 together are -CH=CH-CH=CH-, trimethylene, tetramethylene, -O-CH2-O-, -O-CF2-O-, -O-CH2-CH2-O-. -N(methyl)-CH2-CH2-0-; the Re radicals together are C2-C6-alkylene, -0-(Ci-C4-alkylene)-0- or -O-CF2-O-; Rg is Ci-C4-a1kyl, cyclopentyl, cyclohexyl, phenyl, methylphenyl, methylbenzyl or benzyl; Rio is -CH2-NR11R12, -CHR9-NR11R12, vinyl, methyl or ethyl; and R11 and R12 are identical radicals, and Rn and R12 are each Ci-C4-alkyl, cyclopentyl, cyclohexyl, phenyl, methylphenyl, methylbenzyl or benzyl, or Rn and R12 together are tetramethylene or 3-oxapentane-1,5-diyl; and the Ri3 are each Ci-C4-alkyl, cyclopentyl, cyclohexyl, phenyl, methylphenyl, methylbenzyl or benzyl. 6. Process for preparing compounds of the formula I, which is characterized in that a compound of the fonnula X secondary phosphine-Q-Hal (X) in which secondary phosphine and Q are each as defined above and Hal is CI, Br or I is reacted with a metallating reagent and thereafter with a halophosphine of the fonnuia XI Hal-PX2Ri (XI), in which Ri is as defined in formula I including the preferences, Hal is Cf, Br or I, and X2 is CI, Br, I, Ci-C4-alkoxy or (Ci-C4-alkyl)2amino, and the compound of the formula XII formed secondary phosphine-Q-PX2Ri (XII) Is hydrolysed vwth water to give a compound of the formula I. 8. Metal complexes of transition metals of the transition groups of the Periodic Table of the Elements with a compound of the formula I as a ligand. 9. Process for preparing chiral organic compounds by asymmetric addition of hydrogen to a carbon or carbon-heteroatom double bond in prochiral organic compounds in the presence of a catalyst, which is characterized in that the addition Is performed in the presence of catalytic amounts of at least one metal complex according to Claim 8. 10. Use of the metal complexes according to Claim 8 as homogeneous catalysts for preparing chiral organic compounds by asymmetric addition of hydrogen to a carbon or carbon-heteroatom double bond In prochiral organic compounds. |
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| Patent Number | 268789 | |||||||||||||||||||||
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| Indian Patent Application Number | 7072/CHENP/2008 | |||||||||||||||||||||
| PG Journal Number | 38/2015 | |||||||||||||||||||||
| Publication Date | 18-Sep-2015 | |||||||||||||||||||||
| Grant Date | 16-Sep-2015 | |||||||||||||||||||||
| Date of Filing | 22-Dec-2008 | |||||||||||||||||||||
| Name of Patentee | SOLVIAS AG | |||||||||||||||||||||
| Applicant Address | Romerpark 2,4303 Kaiseraugst, Switzerland | |||||||||||||||||||||
Inventors:
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| PCT International Classification Number | C07F9/46 | |||||||||||||||||||||
| PCT International Application Number | PCT/EP07/55026 | |||||||||||||||||||||
| PCT International Filing date | 2007-05-23 | |||||||||||||||||||||
PCT Conventions:
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