Introduction

The present invention relates to a process for the hydrogenation of imines with hydrogen under elevated pressure in the presence of iridium complexes as catalysts and one or more co-catalysts in a catalytic effective amount selected among compounds comprising a carbon-halogen bond. The invention further relates to certain novel ligands and metal complexes thereof useful for the catalytic hydrogenation of imines.

Background of the invention

Processes for the catalytic hydrogenation of imines have been described in prior art literature. By example, United States patent no. US 4,994,615 describes a process for the asymmetric hydrogenation of prochiral imines wherein homogene iridium based catalysts having chiral diphosphine ligands are used; US patent no. 5,1 12,999 discloses polynuclear iridium compounds and a complex salt of iridium, which contain diphosphine ligands, as catalysts for the hydrogenation of imines; United States patent no. US 6,822,118 describes a process for the asymmetric hydrogenation of prochiral imines with an iridium catalyst in the presence of an ammonium or metal halide and an acid; US patent no. 5,859,300 describes a process for the asymmetric hydrogenation of prochiral imines in the presence of an ammo- nium or metal halide and at least one solid acid with the exception of ion exchangers; US patent no. 5,886,225 describes a process for the asymmetric hydrogenation of prochiral imines with an iridium catalyst in the presence of hydroiodic acid (HI) and International patent application no. WO 2007/414769-A1 teaches asymmetric hydrogenation of prochiral imines under elevated pressure in the presence of iridium based catalysts and a phosphonium halide. Among several others, United States patent no. US 5,565,594 disclose iridium or rhodium based catalysts comprising ferrocene diphosphines as ligands for homogeneous catalysis. United States patent nos. US 5,244,857; US 5,252,751 US 5,306,853 and US 5,382,729 disclose iridium based catalysts comprising ligands fixed to an inorganic support material such as silicates whereas as International patent application no. WO 97/02232-A1 further suggest that addition of an ammonium or metal halides and at least one acid to the reaction mixtures comprising such heterogeneous iridium based catalysts may improve selectivity and catalyst activity.

Those prior catalysis processes have proved valuable, although it is evident, especially in the case of relatively large batches or on an industrial scale, that the catalysts frequently tend to become deactivated to a greater or lesser extent depending on the catalyst precursor, the substrate and the diphosphine ligands that are used. To prevent the catalyst from being deactivated compounds such as ammonium salts, e.g. ammonium iodide, phosphonium hal- ides or acids have been suggested as additives to the reaction mixture. Description of the invention

It has now been found, surprisingly, that a comparable catalyst activity can be retained or even increased when the reaction mixture comprises one or more compounds comprising a carbon-halogen bond. Hence, the present invention relates to a process for the hydrogena- tion of imines with hydrogen under elevated pressure in the presence of iridium based cata- lysts, optionally in the presence of an inert solvent, wherein the reaction mixture comprises in a catalytic effective amount comprises one or more co-catalysts selected among one or more compounds comprising a carbon-halogen bond whereby the reaction rate and or turnover number of the iridium based catalyst is increased.

Suitable imines are especially those that contain at least one group

If the groups are substituted asymmetrically and are thus compounds having a prochiral ketimine group, it is possible in the process according to the invention for mixtures of optical isomers or pure optical isomers to be formed if enantioselective or diastereo-selective iridium catalysts are used. The imines may contain further chiral carbon atoms. The free bonds in the above formulae may be saturated with hydrogen or organic radicals having from 1 to 22 carbon atoms or organic hetero radicals having from 1 to 20 carbon atoms and at least one hetero atom from the group O, S, N and P. The nitrogen atom of the group

may also be saturated with NH ₂ or a primary amino group having from 1 to 22 carbon at- oms or a secondary amino group having from 2 to 40 carbon atoms. The organic radicals may be substituted, for example, by F, Cl, Br, CpC ₄ haloalkyl wherein halogen is preferably F or Cl, -CN, -NO ₂ , -CO ₂ H, -CONH ₂ , -SO ₃ H, -PO ₃ H ₂ , or C _r Ci ₂ alkyl esters or amides, or by phenyl esters or benzyl esters of the groups -CO ₂ H, -SO ₃ H and -PO ₃ H ₂ . Aldimine and ketimine groups are especially reactive, with the result that using the process according to the invention it is possible selectively to hydrogenate

groups in addition to the -C=C- and/or C=O groups. Aldimine and ketimine groups are also to be understood to include

hydrazone and oxime groups.

The process according to the invention is suitable especially for the hydrogenation of aldi- mines, ketimines and hydrazones with the formation of corresponding amines and hydrazines, respectively. The ketimines are preferably N-substituted. It is preferable to use chiral iridium catalysts and to hydrogenate prochiral ketimines to prepare chiral isomers with optical purity (enantiomeric excess, ee) being, for example, higher than 50%, preferably higher than 70%, and conversions of more than 80% being achievable.

The imines are preferably imines of formula (I)

which are hydrogenated to form amines of formula (II)

wherein

R. ₃ is linear or branched Ci-C^alkyl, C ₃ -Cgcycloalkyl, heterocycloalkyl bonded via a carbon atom and having from 3 to 8 ring atoms and 1 or 2 hetero atoms from the group O, S and NR^, a C ₇ -Ci ₆ aralkyl bonded via an alkyl carbon atom or CpC^alkyl substituted by the mentioned cycloalkyl or heterocycloalkyl or heteroaryl; or wherein

R ₃ is C ₆ -Ci ₂ aryl, or C ₃ -Cπheteroaryl bonded via a ring carbon atom and having 1 , 2 or 3 he- tero atoms in the ring; and in either case the aforementioned R ₃ groups being unsubstituted or substituted by one or more substitu- ents, e.g. by -CN, -NO ₂ , F, Cl, Ci-C ₁₂ alkyl, C _r Ci ₂ alkoxy, C _r Ci ₂ alkylthio, C _r Ci ₂ haloalkyl, -OH, C ₆ -C _]2 aryl or -aryloxy or -arylthio, C ₇ -Ci ₆ -aralkyl or -aralkoxy or -aralkylthio, secondary amino having from 2 to 24 carbon atoms, -CONR ₄ R ₅ or by -COOR ₄ , and the aryl radicals and the aryl groups in the aralkyl, aralkoxy and aralkylthio in turn being unsubstituted or substituted by one or more substituents, e.g. selected among -CN, -NO ₂ , halogen (e.g. F or Cl), C,-C ₄ -alkyl, -alkoxy or -alkylthio, -OH, -CONR ₄ R ₅ or by -COOR ₄ ;

R ₄ and R ₅ are each independently of the other hydrogen, CpCnalkyl, phenyl or benzyl, or R ₄ and R ₅ together are tetra- or penta-methylene or 3-oxapentylene;

Ri and R ₂ are each independently of the other a hydrogen atom, Ci-C ₎₂ alkyl or C ₃ - Cgcycloalkyl, each of which is unsubstituted or substituted independently of the other by one or more substituents, e.g. by -OH, Ci-C _]2 alkoxy, phenoxy, benzyloxy, secondary amino having from 2 to 24 carbon atoms, -CONR ₄ R ₅ or by -COOR ₄ ; or C ₆ -C ₁₂ aryl, C ₇ -Ci ₆ aralkyl that is unsubstituted or substituted as R ₃ ; or

R ₃ is as defined hereinbefore and Ri and R ₂ together represents an alkylene bridge having from 2 to 6 carbon atoms that is optionally interrupted by 1 or 2 -O-, -S- or -NR ₆ - radicals, and/or unsubstituted or substituted by =O or as Ri and R ₂ above in the meaning of alkyl, and/or condensed with benzene, pyridine, pyrimidine, furan, thiophene or pyrrole; or

R ₂ is as defined hereinbefore and Ri and R ₃ together represents an alkylene bridge having from 2 to 6 carbon atoms that is optionally interrupted by 1 or 2 -O-, -S- or -NR ₆ - radicals, and/or unsubstituted or substituted by =O or as Ri and R ₂ above in the meaning of alkyl, and/or condensed with benzene, pyridine, pyrimidine, furan, thiophene or pyrrole.

R ₆ represents hydrogen, CpC] ₂ alkyl, phenyl or benzyl.

The radicals Ri, R ₂ and R ₃ may contain one or more chiral centers.

Ri, R ₂ and R ₃ can be substituted in any positions by identical or different radicals, for example by from 1 to 5, preferably from 1 to 3, substituents. Suitable substituents for R ₁ , R ₂ and/or R ₃ are:

Ci-Ci ₂ -, preferably CpC ₆ -, and especially Ci-C ₄ -alkyl, -alkoxy or -alkylthio, e.g. methyl, ethyl, propyl, n-, i- and f-butyl, the isomers of pentyl, hexyl, octyl, nonyl, decyl, undecyl and dodecyl, and corresponding alkoxy and alkylthio radicals; Cj-Cg-, preferably Ci-Gj-haloalkyl having preferably F and Cl as halogen, e.g. trifluoro- or trichloro-methyl, difluorochloromethyl, fluorodichloromethyl, 1,1-difluoroeth-l-yl, 1 , 1 -dichloroeth- 1 -yl, 1 , 1 , 1 -trichloro- or l,l,l-trifluoroeth-2-yl, pentachloroethyl, penta-fluoroethyl, 1,1,1-trifluoro- 2,2-dichloroethyl, w-perfluoropropyl, zso-perfluoropropyl, «-perfluorobutyl, fluoro- or chloro-methyl, difluoro- or dichloro-methyl, 1 -fluoro- or l-chloro-eth-2-yl or -eth-l-yl, 1-, 2- or 3-fluoro- or 1-, 2- or 3-chloro-prop-l-yl or -prop-2-yl or -prop-3-yl, 1 -fluoro- or 1-chloro-but-l-yl, -but-2-yl, -but-3-yl or -but-4-yl, 2,3-dichloro- prop-1-yl, l-chloro-2-fluoro-prop-3-yl, 2,3-dichlorobut-l-yl; -aryloxy or -arylthio, in which aryl is preferably naphthyl and especially phenyl, C ₇ -Ci ₆ -aralkyl, -aralkoxy and -aralkylthio, in which the aryl radical is preferably naphthyl and especially phenyl and the alkylene radical is linear or branched and contains from 1 to 10, preferably from 1 to 6 and especially from 1 to 3, carbon atoms, for example benzyl, naphthylmethyl, 1- or 2-phenyl-eth-l-yl or - eth-2-yl, 1 -, 2- or 3-phenyl-prop-l-yl, -prop-2-yl or -prop-3-yl, with benzyl being especially preferred; the radicals containing the aryl groups mentioned above may in turn be mono- or poly-substituted, for example by C _r C ₄ -alkyl, -alkoxy or -alkylthio, halogen, -OH, - CONR ₄ R ₅ or by -COOR ₄ , R ₄ and R ₅ are as defined above and examples are methyl, ethyl, n- and iso-propyl, butyl, corresponding alkoxy and alkylthio radicals, F, Cl, Br, dimethyl-, methyl-ethyl- and diethyl-carbamoyl and methoxy-, ethoxy-, phenoxy- and benzyloxy- car- bonyl; halogen, preferably F and Cl; secondary amino having from 2 to 24, preferably from 2 to 12 and especially from 2 to 6 carbon atoms, the secondary amino preferably containing 2 alkyl groups, for example dimethyl-, methylethyl-, diethyl-, methylpropyl-, methyl-«- butyl-, di-M-propyl-, di-n-butyl-, di-«-hexyl- amino;

-CONR ₄ R ₅ , wherein R ₄ and R ₅ are each independently of the other C ₁ -Ci ₂ -, preferably C _r C ₆ -, and especially Ci-C ₄ -alkyl, or R ₄ and R ₅ together are tetra- or penta-methylene or 3- oxapentylene, the alkyl being linear or branched, e.g. dimethyl-, methylethyl-, diethyl-, me- thyl-tt-propyl-, ethyl-H-propyl-, di-w-propyl-, methyl-rc-butyl-, ethyl-w-butyl-, rc-propyl-M- butyl- and di-rc-butyl-carbamoyl;

-COOR ₄ , wherein R ₄ is Ci-Ci ₂ , preferably CpC _ό -alkyl, which may be linear or branched, e.g. methyl, ethyl, n- and /-propyl, n-, i- and /-butyl, and the isomers of pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl.

Ri, R ₂ and R ₃ may contain especially functional groups, such as keto groups, -CN, -NO ₂ , carbon double bonds, N-O-, aromatic halogen groups and amide groups.

Heteroaryl Ri, R ₂ or R ₃ are preferably a 5- or 6-membered ring having 1, 2 or 3 identical or different hetero atoms, especially O, S or N, which contains preferably 4 or 5 carbon atoms and can be condensed with benzene. Examples of heteroaromatics from which Ri or R ₂ can be derived are furan, pyrrole, thiophene, pyridine, pyrimidine, indole, quinoline and triazole.

Ri, R ₂ or R ₃ as heteroaryl-substituted alkyl are derived preferably from a 5- or 6-membered ring having 1 or 2 identical or different hetero atoms, especially O, S or N, which contains preferably 4 or 5 carbon atoms and can be condensed with benzene. Examples of heteroaromatics are furan, pyrrole, thiophene, pyridine, pyrimidine, indole and quinoline.

Ri, R ₂ or R ₃ as heterocycloalkyl or as heterocycloalkyl-substituted alkyl contain preferably 5 or 6 ring atoms and 1 , 2 or 3 identical or different hetero atoms from the group O, S and NR ₆ , wherein R ₆ is as defined above and examples of Re include hydrogen, phenyl or benzyl. They can be condensed with benzene. It may be derived, for example, from pyrrolidine, tetrahydrofuran, triazole, tetrahydrothiophene, indane, pyrazolidine, oxazolidine, piperidine, piperazine or morpholine. Alkyl R ₁ , R ₂ or R ₃ are preferably unsubstituted or substituted by C]-Ce-, especially by Cr Q-alkyl, which may be linear or branched. Examples are methyl, ethyl, i- and rc-propyl, /-, n- and /-butyl, the isomers of pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl.

Unsubstituted or substituted cycloalkyl Ri, R ₂ or R ₃ contain preferably from 3 to 6, especially 5 or 6, ring carbon atoms. Examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclo- hexyl, cycloheptyl and cyclooctyl.

R ₁ , R ₂ or R ₃ as aryl are preferably unsubstituted or substituted naphthyl and especially phenyl.

Ri, R ₂ or R ₃ as aralkyl are preferably unsubstituted or substituted phenylalkyl having from 1 to 10, preferably from 1 to 6 and especially from 1 to 4 carbon atoms in the alkylene, the al- kylene being linear or branched. Examples are especially benzyl, and 1-phenyleth-l-yl, 2- phenyleth-1 -yl, 1 -phenylprop-1-yl, l-phenylprop-2-yl, l-phenyl-prop-3-yl, 2-phenylprop-l-yl, 2-phenylprop-2-yl and l-phenylbut-4-yl.

In -CONR ₄ R ₅ and -COOR ₄ , R ₄ and R ₅ are preferably C ₁ -C ₆ -, especially Ci-C ₄ -alkyl, or R ₄ and R ₅ together are tetramethylene, pentamethylene or 3-oxapentylene.

Alkylene Ri and R ₂ together or R ₁ and R ₃ together are preferably interrupted by 1 -O-, -S- or -NR ₆ -, preferably -O-. Ri and R ₂ together or Ri and R ₃ together form, with the carbon atom or with the -N=C group to which they are bonded, respectively, preferably a 5- or 6- membered ring. For the substituents the preferences mentioned hereinbefore apply. As condensed alkylene, Ri and R ₂ together or Ri and R ₃ together are preferably alkylene condensed with benzene or pyridine. Examples of alkylene are: ethylene, 1,2- or 1,3 -propylene, 1,2-, 1,3- or 1 ,4-butylene, 1,5-pentylene and 1 ,6-hexylene. Examples of interrupted or =0- substituted alkylene are 2-oxa- 1,3 -propylene, 2-oxa- 1 ,4-butylene, 2-oxa- or 3-oxa-l,5- pentylene, 2-methylimino-l,3-propylene, 3-thia- 1,5-pentylene, 2-thia-l,4-butylene, 2-thia- 1,3-propylene, 2-ethylimino-l,4-butylene, 2- or 3-methyl-imino- 1,5-pentylene, l-oxo-2-oxa- 1,3-propylene, l-oxo-2-oxa-l,4-butylene, 2-oxo-3-oxa-l,4-butylene, l-oxa-2-oxo- 1,5- pentylene. R ₄ and R ₅ are preferably each independently of the other hydrogen, Ci-C ₄ alkyl, phenyl or benzyl.

R _O is preferably hydrogen or Ci-C ₄ alkyl.

Another preferred group is formed by prochiral imines in which in formula (I) Ri, R ₂ and R3 are each different from the others and are not hydrogen. In an especially preferred group, in formula (I) R ₃ is 2,6-di-Ci-C ₄ alkylphen-l-yl or 2,4-di- Ci-C ₄ alkylthiophen-3-yl and especially 2,6-dimethylphen-l-yl, 2-methyl-6-ethylphen-l-yl or 2,4-dimethylthiophen-3-yl, R, is Ci-C ₄ alkyl and especially ethyl or methyl, and R ₂ is Cp C ₄ alkyl, C _r C ₄ alkoxymethyl or C _r C ₄ alkoxyethyl, and especially methoxymethyl.

Of those compounds, imines of formulae (Ia), (Ib) and (Ic)

are especially important. Imines of formula (I) are known or they can be prepared in accordance with known processes from aldehydes or ketones and primary amines.

The iridium based catalysts are preferably homogeneous catalysts that are substantially so- luble in the reaction medium, but may also be bound to an inorganic support material such as silicates. The term "catalyst" also includes catalyst precursors that are converted into an active catalyst species at the beginning of a hydrogenation. The catalysts may correspond to the formulae (IV), (IVa), (IVb), (IVc) or (IVd): [XIrYZ] (IV)

[XIrY] ⁺ A ^" (IVa)

[YIrZ ₄ ] ^" M ⁺ (IVb)

[YIrHZ ₂ J ₂ (IVc) [YIrZ ₃ J ₂ (IVd)

[YIrZH(A)] (IVe)

[YIrH(A) ₂ ] (IVf)

[YIr(A) ₃ ] (IVg) wherein X is two olefin ligands or a diene ligand, Y is a ditertiary diphosphine (a) the phosphine groups of which are bonded to different carbon atoms of a carbon chain having from 2 to 4 carbon atoms, or

(b) the phosphine groups of which are either bonded directly or via a bridge group -CR ₃ Rt,- in the ortho positions of a cyclopentadienyl ring or are each bonded to a cyclopentadienyl ring of a ferrocenyl, or (c) one phosphine group of which is bonded to a carbon chain having 2 or 3 carbon atoms and the other phosphine group of which is bonded to an oxygen atom or a nitrogen atom bonded terminally to that carbon chain, or

(d) the phosphine groups of which are bonded to the two oxygen atoms or nitrogen atoms bonded terminally to a C ₂ -carbon chain; with the result that in the cases of (a), (b), (c) and (d) a 5-, 6-, 7-, 8- or 9-membered ring is formed together with the Ir atom; the radicals Z are each independently of the other(s) Cl, Br or I;

A is the anion of an oxy or complex acid;

M ⁺ is cation such as a phosphonium, a metal or a quaternary ammonium cation; and R ₃ and R _b , are each independently of the other hydrogen, Q-C^alkyl, Ci-C ₄ fluoroalkyl, C ₃ - Cgcycloalkyl, C ₆ -Ci ₂ aryl or C ₃ -Ci ₂ heteroaryl having heteroatoms selected from the group consisting of O, S and N, which are unsubstituted or substituted independently by the others by one or more substituents, e.g. by Ci-C ₆ alkyl, d-C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, CrCgcycloalkoxy, phenyl, Ci-C ₆ alkylphenyl, Ci-C ₆ -alkoxy-phenyl, C ₃ -Cgheteroaryl or halogen. R _b is preferably hydrogen. The diphosphine Y contains preferably at least one chiral carbon atom and is especially a single stereoisomer (enantiomer or diastereoisomer), or a pair of diastereoisomers. The use of catalysts containing those ligands leads to optical induction in hydrogenation reactions.

X as an olefin ligand may be a branched or, preferably, linear C ₂ -Ci ₂ alkylene, especially C ₂ - Cβalkylene. Some examples are dodecylene, decylene, octylene, 1-, 2- or 3-hexene, 1-, 2- or 3- pentene, 1- or 2-butene, propene and ethene.

X as a diene ligand may be open-chain or cyclic dienes having from 4 to 12, preferably from 5 to 8, carbon atoms, the diene groups preferably being separated by one or two saturated carbon atoms. Some examples are butadiene, pentadiene, hexadiene, heptadiene, octa- diene, decadiene, dodecadiene, cyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooc- tadiene and bridged cyclo-dienes such as norbornadiene and bicyclo-2,2,2-octadiene. Hexadiene, cyclooctadiene (cod) and norbornadiene are preferred.

The phosphine groups contain two identical or different unsubstituted or substituted hydrocarbon radicals having from 1 to 20, especially from 1 to 12 carbon atoms. Preference is given to diphosphines wherein the secondary phosphine groups contain two identical or different radicals from the following group: linear or branched CrC ₁₂ alkyl; unsubstituted or C _r C ₆ alkyl- or C _r C ₆ alkoxy-substituted C ₅ -Ci ₂ -cycloalkyl, C ₅ -Ci ₂ cycloalkyl-CH ₂ -, phenyl or benzyl; and phenyl or benzyl substituted by halogen, Ci-C _ό haloalkyl, (C _r C ₁₂ alkyl) ₃ Si, (Ce- C ₁₂ aryl) ₃ Si, C _r C ₆ haloalkoxy (e.g. trifluoromethoxy), -NH ₂ , (phenyl) ₂ N-, (benzyl) ₂ N-, mor- pholinyl, piperidinyl, pyrrolidinyl, (Ci -C _h alky I) ₂ N-, (C ₇ -C ₁₂ aralky I) ₂ N-, -ammonium-Xi, - SO ₃ M ₁ , -CO ₂ M ₁ , -PO ₃ M, or by -COO-C ₁ -C ₆ -alkyl (e.g. -COOCH ₃ ), wherein M ₁ is an alkali metal or hydrogen and X ₁ is the anion of a monobasic acid. M ₁ is preferably H, Li, Na or K. X ₁ , as the anion of a monobasic acid, is preferably Cl, Br or the anion of a carboxylic acid, for example formate, acetate, trichloroacetate or trifluoroacetate. A secondary phosphine group may also be a radical of the formulae

wherein the rings may be substituted by, e.g., CpCβ-alkyl, d-C ₆ -alkoxy, Ci-C ₆ -alkoxy-Ci-C ₆ -alkyl, phenyl, benzyl, benzyloxy or CpCe-alkylidenedioxyl or Ci-Cβ-alkylenedioxyl and wherein m and n are each independently of the other an integer from 1 to 10, and the sum of m+n is from 1 to 12, especially from 4 to 8. Examples thereof are [3.3.1]- and [4.2.1]-phobyl of the formulae

Examples of alkyl that preferably contains from 1 to 6 carbon atoms are methyl, ethyl, n- propyl, isopropyl, n-, i- and /-butyl and the isomers of pentyl and hexyl. Examples of unsub- stituted or alkyl-substituted cycloalkyl are cyclopentyl, cyclohexyl, methyl- or ethyl- cyclohexyl and dimethylcyclohexyl. Examples of alkyl-, alkoxy- or haloalkoxy-substituted phenyl and benzyl are methylphenyl, dimethylphenyl, trimethylphenyl, ethyl-phenyl, me- thylbenzyl, methoxyphenyl, dimethoxyphenyl, trifiuoromethylphenyl, bis-tri- fluoromethylphenyl, trifluoromethoxyphenyl and bis-trifluoro-methoxyphenyl. Preferred phosphine groups are those that contain identical or different, preferably identical, radicals from the group Ci-C ₆ alkyl; cyclopentyl and cyclohexyl that are unsubstituted or have from 1 to 3 C]-C ₄ alkyl or C _r C ₄ alkoxy substituents, benzyl and, especially, phenyl that is unsub- stituted or has from 1 to 3 Q-Qalkyl, C _r C ₄ alkoxy, F, Cl, C _r C ₄ fluoroalkyl or C _r Qfluoroalkoxy substituents.

Examples of secondary non-cyclic phosphine groups include -P(Ci-C ₆ -alkyl) ₂ , -P(Cs-Cg- cycloalkyl) ₂ , -P(C ₇ -C, ₂ -bicycloalkyl) ₂ , -P(o-furyl) ₂ , -P(C ₄ Hj) ₂ , -P[2-(C,-C ₆ -alkyl)C ₆ H ₄ ] ₂ , - P[3-(C,-C ₆ -alkyl)C ₆ H ₄ ] ₂ , -P[4-(C _r C ₆ -alkyl)C ₆ H ₄ ] ₂ , -P[2-(C,-C ₆ -alkoxy)C ₆ H ₄ ] ₂ , -P[3-(C,- C ₆ -alkoxy)C ₆ H ₄ ] ₂ , -P[4-(Ci-C ₆ -alkoxy)C ₆ H ₄ ] ₂ , -P[2-(trifluoromethyl)C ₆ H ₄ ] ₂ , -P[3- (trifluoromethyl)C ₆ H ₄ ] ₂ , -P[4-(trifluoromethyl)C ₆ H ₄ ] ₂ , -P[3,5-bis(trifluoromethyl)C ₆ H ₃ ] ₂ , - P[3,5-bis(CrC ₆ -alkyl) ₂ C ₆ H ₃ ] ₂ , -P[3,5-bis(C,-C ₆ -alkoxy) ₂ C ₆ H ₃ ] ₂ , -P[3,5-bis(C,-C ₆ -alkyl) ₂ -4- (C,-C ₆ -alkoxy)C ₆ H ₂ ] ₂ and -P[3,4,5-tris(C,-C ₆ -alkoxy) ₂ C ₆ H ₃ ] ₂ .

Depending on the type of substitution and the number of substituents, the cyclic phosphine groups can be C-chiral, P-chiral or C- and P-chiral.

Examples of secondary cyclic phosphine groups can correspond to the following formulae: where the substituents R' and R" are identical or different and may each represent hydrogen, Ci-C ₆ alkyl, for example methyl, ethyl, n- or /-propyl, benzyl, or -CH ₂ -O-C rC ₆ alky I or - CH ₂ -O-C ₆ -C _l0 aryl, and R' and R" are identical or different. When R' and R" are bound to the same carbon atom, they can together form a C ₄ -C ₆ alkylene group. In the above formulae, when applicable e.g. when R' and R" are not both H or identical and at the same time attached to the same carbon atom, only one of the possible diastereomers of each formula is indicated.

Y as a diphosphine may be represented by one of formula (V), (Va), (Vb), (Vc), (Vd) or (Ve),

R ₇ R ₈ P-R ₉ -PRiORn (V), R ₇ RgP-O-Rn-PRiORn (Va), R ₇ R ₈ P-NR ₀ R ₁₂ -PRiORiI (Vb), R ₇ R ₈ P-O-RI ₃ -O-PR ₁₀ RI I (Vc),

R ₇ R ₈ P-NRc-R ₁₃ -NRe-PR ₁₀ Ri , (Vd),

R ₇ R ₈ P-NRe-R ₉ -PR ₁₀ Ri , (Ve) wherein R ₇ , R ₈ , Ri ₀ and R _{1 I} each independently of the others represent C]-C ₁₂ alkyl, C,-C, ₂ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ cycloalkoxy, C ₆ -C, ₂ aryl, C ₃ - C, ₂ heteroaryl, C ₆ -C i ₂ aryl-C, -C , ₂ alkoxy- or Cj-Cnheteroaryl-C]- C ₁₂ alkyl- having heteroatoms selected from the group consisting of O, S and N, the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by Ci-Cβalkyl, CpCβalkoxy, Cs-Cgcycloalkyl, C ₃ -C ₈ cycloalkoxy, phenyl, phenyl-Ci-C ₆ alkyl- (e.g. benzyl), phenyl-Ci-C ₆ alkoxy-, C ₃ -Cgheteroaryl, (Ci-Ci ₂ aikyl) ₃ Si, (C ₆ -Ci ₂ aryl) ₃ Si, -NH ₂ , (phenyl) ₂ N-, (benzyl) ₂ N-, moφholinyl, piperidinyl, pyrrolidinyl, (C,-Ci ₂ alkyl) ₂ N-, (C ₇ -C, ₂ aralky I) ₂ N-, C,-Ci ₂ haloalkyl, C,-Ci ₂ haloalkoxy, halogen, -ammonium-Xi, -SO ₃ M ₁ , -CO ₂ Mi, -PO ₃ Mi or by -COO-Ci-Qalkyl, wherein Mi is an alkali metal or hydrogen and Xi is the anion of a monobasic acid. Mi is preferably H, Li, Na or K. X ₁ , as the anion of a monobasic acid, is preferably Cl, Br or the anion of a carboxylic acid, for example formate, acetate, trichloroacetate or trifluoroacetate; or R ₇ and Rg together or R ₁₀ and R _{1 1} together represents an alkylene bridge having from 2 to 6 carbon atoms that is optionally interrupted by 1 or more -0-, -S- or -NR ₆ - comprising radicals such as N-H, N-CrC ₁₂ alkyl or N-C ₆ -C ₁₂ aryl; and may be unsubstituted or substituted by =0 or by one or more groups of Q-Qalkyl, CpQalkoxy, C ₃ -Cgcycloalkyl, C ₃ -Cscycloalkoxy, phenyl, phenyl-CrC ₆ alkyl-, phenyl-C _r C ₆ alkoxy-, or halogen groups; and/or condensed with benzene, pyridine, pyrimidine, furan, thiophene or pyrrole;

Preferably R ₇ , Rg, R] ₀ and Rn, are identical or different, most preferably identical, radicals selected from the following group: C _r C ₆ alkyl; C ₄ -C ₆ cycloalkyl that are unsubstituted or have from 1 to 3 C]-C ₄ alkyl or Ci-C ₄ alkoxy substituents; phenyl or benzyl, especially phenyl, that is unsubstituted or has from 1 to 3 Ci-C ₄ alkyl, Ci-C ₄ alkoxy, F, Cl, C ₁ - C ₄ fluoroalkyl or Ci-C ₄ fluoroalkoxy substituents.

R ₇ , Rg, Rio and Rn can be substituted in any positions by identical or different radicals, for example by from 1 to 5, preferably from 1 to 3, substituents

R ₉ is linear C ₂ -C ₄ alkylene that is unsubstituted or substituted by C _r C ₆ alkyl, C ₃ -C ₆ -cycloalkyl, phenyl, naphthyl or by benzyl; 1,2- or 1 ,3-cycloalkylene or -cycloalkenylene, -bicycloalkylene or -bicycloalkenylene having from 4 to 10 carbon atoms, the aforementioned groups each being unsubstituted or substituted independently of one an- other by one or more substituents, e.g. by C]-C ₆ alkyl, phenyl or by benzyl; 1 ,2- or 1,3- cycloalkylene or -cycloalkenylene, -bicycloalkylene or -bicycloalkenylene having from 4 to 10 carbon atoms, the aforementioned groups each being unsubstituted or substituted independently of one another by one or more substituents, e.g. by Ci-Cβalkyl, phenyl or by benzyl, and in the 1- and/or 2-positions or in the 3-position of which methyl-ene or C ₂ - C ₄ alkylidene is bonded; 1 ,4-butylene substituted in the 2,3-positions by

and unsubstituted or substituted in the 1 ,4-positions by C _r C ₆ alkyl, phenyl or by benzyl, wherein R ₂₁ and R ₂₂ are each independently of the other hydrogen, Ci-C ₆ alkyl, phenyl or benzyl; 3,4- or 2,4-pyrrolidinylene or 2-methylene-pyrrolidin-4-yl the nitrogen atom of which is substituted by hydrogen, C _r Ci ₂ alkyl, phenyl, benzyl, Q- Ci ₂ alkoxycarbonyl, Q-Cgacyl or by or CpCnalkylaminocarbonyl; or 1 ,2-phenylene, 2- benzylene, 1,2-xylylene, 1,8-naphthylene, 2,2'-dinaphthylene or 2,2'-diphenylene, the aforementioned groups each being unsubstituted or substituted independently of one another by one or more substituents. e.g. by Ci-C ₄ alkyl;

R ₁₂ is linear C ₂ - or C ₃ -alkylene that is unsubstituted or substituted e.g. by C|-C ₆ alkyl, C ₃ - C ₆ cycloalkyl, phenyl, naphthyl or by benzyl; 1,2- or 1 ,3-cycloalkylene or -cycloalkenylene, - bicycloalkylene or -bicycloalkenylene having from 4 to 10 carbon atoms, the aforementioned groups each being unsubstituted or substituted independently of the others by one or more groups, e.g. by Ci-C ₆ alkyl, phenyl or by benzyl; or 1,2- or 1,3-cycloalkylene or - cycloalkenylene, -bicycloalkylene or -bicycloalkenylene having from 4 to 10 carbon atoms, the aforementioned groups each being unsubstituted or substituted independently of the others by one or more groups, e.g. by Ci-C ₆ alkyl, phenyl or by benzyl, and in the 1- and/or 2-positions or in the 3-position of which methylene or C ₂ -C ₄ alkylidene is bonded; 3,4- or 2,4-pyrrolidinylene or 3-methylene-pyrrolidin-4-yl the nitrogen atom of which is substituted by hydrogen, C _r Ci ₂ alkyl, phenyl, benzyl, C _r Ci ₂ alkoxycarbonyl, Q-Cgacyl or by C _r C ₎₂ alkylaminocarbonyl; or 1 ,2-phenylene, 2-benzylene, 1,2-, 2,3- or 1 ,8-naphthylene, the aforementioned groups each being unsubstituted or substituted independently of the others by one or more groups, e.g. by Ci-Cβalkyl; and

Rn is linear C ₂ alkylene that is unsubstituted or substituted by Ci-C ₆ alkyl, C ₃ -C ₆ cycloalkyl, phenyl, naphthyl or by benzyl; 1 ,2-cycloalkylene or -cycloalkenylene, - bicycloalkylene or - bicycloalkenylene having from 4 to 10 carbon atoms, each of which is unsubstituted or substituted by one or more groups, e.g. Ci-Cβalkyl, phenyl or by benzyl; 3,4-pyrrolidinylene the nitrogen atom of which is substituted by hydrogen, phenyl, benzyl, C _r C ₁₂ alkoxycarbonyl or by CpCnalkylaminocarbonyl; or 1,2-phenylene that is unsubstituted or substituted by Ci-C ₆ alkyl, or is a radical, less two hydroxy groups in the ortho positions, of a mono- or di-saccharide; and R ₀ is hydrogen, Ci-Cβalkyl, phenyl or benzyl.

R ₉ however, preferably is an optionally substituted ferrocenyl radical, e.g. a radical of the formulae

wherein Ri ₄ and Ri ₅ independently of one another, each represent hydrogen, Ci-C ₂ oalkyl, Ci-C ₄ fluoroalkyl, C ₃ -C ₈ cycloalkyl, C ₆ -Ci ₂ aryl or C ₃ -Ci ₂ heteroaryl having het- eroatoms selected from the group consisting of O, S and N, the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by halogen, OR _0O , NR ₀₇ Ro ₈ , C _r C ₆ alkyl, C _r C ₆ alkoxy, C ₃ -Cgcycloalkyl, C ₃ -C ₈ cycloalkoxy, phenyl, Ci-C ₆ alkylphenyl, C _r C ₆ alkoxy phenyl, C ₃ -C ₈ heteroaryl or halogen; or one of

R] ₄ or Ri ₅ is connected through a bridging group with the adjacent phosphor atom in the secondary phosphine group of which the carbon atom bearing R _]4 and Ri ₅ is attached to (i.e. the phosphor atom in the group R ₇ R ₈ P- or -PRi ₀ Ri ₁ ), e.g. via a Ci-C ₈ alkylene, alkenylene, or alkynylene bridge optionally with one or more of the carbon atoms substituted with a heteroatom, said bridge optionally being substituted with one or more substituents that may be selected among C ₃ -C ₈ cycloalkyl, C ₆ -Ci ₂ aryl or C ₃ -Ci ₂ heteroaryl having het- eroatoms selected from the group consisting of O, S and N, the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by Ci-C ₆ alkyl, C]-C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ -Cgcycloalkoxy, phenyl, Ci-C ₆ alkylphenyl, Ci-Cβalkoxy phenyl or C ₃ -C ₈ heteroaryl; and wherein the cyclopentadienyl rings, independently of one another, may be substituted by one or more substituents, e.g. by a halogen atom, additional secondary phosphine groups as described herein, or a substituent bound to the cyclopentadienyl ring via a C atom, S atom, Si atom, a P(O) group or a P(S) group all of which may carry one or more secondary phosphine groups as herein described; examples of such substituents on the cyclopentadienyl rings are methyl, ethyl, n- and /-propyl, «-, /- and f-butyl, pentyl, hexyl, cyclohexyl, cyclohexyl methyl, phenyl, benzyl, trimethylsilyl, F, Cl, Br, methylthio, methylsulphonyl, methylsulphoxyl, phenylthio, phenylsulphonyl, phenyl- sulphoxyl, -CH(O), -C(O)OH, -C(O)-OCH ₃ , -C(O)-OC ₂ H ₅ , -C(O)-NH ₂ , -C(O)-NHCH ₃ , - C(O)-N(CHs) ₂ , -SO ₃ H, -S(O)-OCH ₃ , -S(O)-OC ₂ H ₅ , -S(O) ₂ -OCH ₃ , -S(O) ₂ -OC ₂ H ₅ , -S(O)- NH ₂ , -S(O)-NHCH ₃ , -S(O)-N(CHa) ₂ , -S(O)-NH ₂ , -S(O) ₂ -NHCH ₃ , -S(O) ₂ -N(CHj) ₂ , -P(OH) ₂ , PO(OH) ₂ , -P(OCH ₃ ) ₂ , -P(OCH ₃ ) ₂ , -PO(OCH ₃ ) ₂ , -PO(OC ₂ H ₅ ) ₂ , trifluoromethyl, methylcy- clohexyl, methylcyclohexylmethyl, methylphenyl, dimethylphenyl, methoxyphenyl, dimeth- oxyphenyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, -CH ₂ NH ₂ , -CH ₂ N(CH ₃ ) ₂ , - CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ N(CH ₃ ) ₂ , methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, HS-CH ₂ -, HS-CH ₂ CH ₂ -, CH ₃ S-CH ₂ -, CH ₃ S-CH ₂ CH ₂ -, -CH ₂ -C(O)OH, -CH ₂ CH ₂ -C(O)OH, -CH ₂ -C(O)OCH ₃ , -CH ₂ CH ₂ -C(O)OCH ₃ , -CH ₂ -C(O)NH ₂ , -CH ₂ CH ₂ -C(O)NH ₂ , -CH ₂ -C(O)- N(CH ₃ ) ₂ , -CH ₂ -SO ₃ H, -CH ₂ CH ₂ -C(O)N(CH ₃ ) ₂ , -CH ₂ CH ₂ -SO ₃ H, -CH ₂ -SO ₃ CH ₃ , -CH ₂ CH ₂ - SO ₃ CH ₃ , -CH ₂ -SO ₂ NH ₂ , -CH ₂ -SO ₂ N(CH ₃ ) ₂ , -CH ₂ -PO ₃ H ₂ , -CH ₂ CH ₂ -PO ₃ H ₂ , -CH ₂ - PO(OCH ₃ ), -CH ₂ CH ₂ -PO(OCH ₃ ) ₂ , -C ₆ H ₄ -C(O)OH, -C ₆ H ₄ -C(O)OCH ₃ , -C ₆ H ₄ -S(O) ₂ OH, - C ₆ H ₄ -S(O) ₂ OCH ₃ , -CH ₂ -O-C(O)CH ₃ , -CH ₂ CH ₂ -O-C(O)CH ₃ , -CH ₂ -NH-C(O)CH ₃ , - CH ₂ CH ₂ -NH-C(O)CH ₃ , -CH ₂ -O-S(O) ₂ CH ₃ , -CH ₂ CH ₂ -O-S(O) ₂ CH ₃ , -CH ₂ -NH-S(O) ₂ CH ₃ , - CH ₂ CH ₂ -NH-S(O) ₂ CH ₃ , -P(O)(C _r C _s alkyl) ₂ , -P(S)(C, -C ₈ alkyl) ₂ , -P(O)(C ₆ -C ₁₀ ary I) ₂ , - P(S)(C ₆ -Ci ₀ aryl) ₂ , -C(O)-C ,-Cgalkyl and -C(O)-C ₆ -C, _o aryl.

V represents an optionally substituted C ₆ -C ₂₀ arylene or C ₃ -C ₁₆ heteroarylene group wherein the connecting bonds to such group are positioned ortho to one another, i.e. on adjacent carbon atoms in the ring structure. An arylene group V preferably contains from 6 to 14 carbon atoms. Examples of arylene are phenylene, naphthylene, anthracylene and phenanthrylene. Preference is given to phenylene and naphthylene. A heteroarylene group V preferably contains from 5 to 14 carbon atoms. The heteroatoms are preferably selected from the group consisting of O, S and N. The heteroarylene can contain from 1 to 4, preferably 1 or 2, identical or different heteroatoms. A few examples are pyridinylene, pyrimidinylene, pyrazinylene, pyrrolylene, furanylene, oxazolylene, imidazolylene, benzofuranylene, indolylene, benzimidazolylene, quinolylene, isoquinolylene, quinazolinylene and quinoxalinylene. When substituted the arylene or heteroarylene group may be substituted by one or more identical or different groups e.g. Ci-C ₄ alkyl, Q-C ₄ alkoxy, Ci-C ₄ fluoroalkyl or Ci-C ₄ fluoroalkoxy. R ₀₀ represents H, C,-C ₁₂ alkyl, Q-Q ₂ alkenyl, C,-Ci ₂ alkynyl, C ₃ -C ₈ cycloalkyl, C ₆ -C, ₂ aryl, R _0I Ro ₂ R ₀₃ Si, C ₁ -Ci _S aCyI that is optionally substituted, e.g. by halogen, hydroxy, Q- C ₈ alkoxy or R ₀₄ PM) ₅ N-, or R ₀₀ represents R ₀₆ -Xo _I -C(O)-; R ₀ ,, R ₀₂ and R ₀₃ are each, independently of one another, Q-Q ₂ alkyl, unsubstituted or C _r C ₄ alkyl, Ci-C ₄ haloalkyl or Q- Qalkoxy-substituted C ₆ -Q ₀ aryl or C ₇ -Q ₂ aralkyl; R ₀₄ and R ₀₅ are each, independently of one another, hydrogen, C _r Ci ₂ alkyl, C ₃ -C ₈ cycloalkyl, C ₆ -Ci ₀ aryl or C ₇ -Ci ₂ -aralkyl, or R ₀₄ and R _0S together are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; R ₀₆ is Ci-Ci ₈ alkyl, unsubstituted or Ci-C ₄ alkyl- or C]-C ₄ alkoxy-substituted C ₃ -Cscycloalkyl, Cβ- Cioaryl or C ₇ -Ci ₂ aralkyl; X ₀ ] is -O- or -NH-; all the aforementioned groups being unsubsti- tuted or substituted independently of the others by one or more substituents e.g. by halogen, Ci-C ₆ alkyl, Ci-C ₆ alkoxy, C ₃ -Cgcycloalkyl, C ₃ -C ₈ cycloalkoxy, phenyl, C _r C ₆ alkyl phenyl, CpCβalkoxy phenyl, C ₃ -C ₈ heteroaryl.

R ₀₇ and R _0S independently of one another represents hydrogen, CpCnalkyl, C ₃ -C ₈ cycloalkyl, C ₆ -Ci ₀ aryl or C ₇ -Ci ₂ aralkyl, or R ₀₇ and R ₀₈ together are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by halogen, Ci-C ₆ alkyl, C _r C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ cycloalkoxy, phenyl, Ci-C ₆ alkyl phenyl, CpC _ό alkoxy phenyl, C ₃ -C ₈ heteroaryl.

Alkyl groups, e.g. R ₀₁ , R ₀₂ and Ro ₃ , can be linear or branched and the alkyl preferably has from 1 to 12 carbon atoms, particularly preferably from 1 to 4 carbon atoms. Aryl groups

Roi, R ₀₂ and R ₀₃ can be, for example, phenyl or naphthyl and aralkyl groups R ₀ I, R02 and

Ro ₃ can be benzyl or phenylethyl. Some examples Of R ₀₁ , R ₀₂ and Ro ₃ are methyl, ethyl, n- or /-propyl, n- , /- or /-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, phenyl, benzyl, methylphenyl, methylbenzyl, methoxyphenyl, dimethoxyphenyl and meth- oxybenzyl.

Some preferred examples of silyl groups RoiRo ₂ Ro ₃ Si are trimethylsilyl, tri-«-butylsilyl, ?-butyldimethylsilyl, 2,2,4,4,-tetramethylbut-4-yl-yldimethylsilyl, triphenyl- silyl and tri-i-propylsilyl

In a preferred embodiment, R ₀₄ and R ₀₅ are each, independently of one another, hydrogen, Q-C ₄ alkyl, C ₅ -C ₆ cycloalkyl, phenyl or benzyl, or R ₀₄ and R ₀₅ together are tetramethylene, pentamethylene or 3-oxapentyl-l ,5-ene. The substituent Ci-C ₈ alkoxy is preferably Cp C ₄ alkoxy such as methoxy, ethoxy, propoxy or butoxy.

An acyl group, e.g. as defined for R ₀₀ , preferably has from 1 to 12 carbon atoms, particularly preferably from 1 to 8 carbon atoms, and is, in particular, derived from a carboxylic acid. Examples of such carboxylic acids are aliphatic, cycloaliphatic and aromatic carboxylic acids having from 1 to 18 carbon atoms, preferably from 1 to 12 carbon atoms. Some examples of acyl are acetyl, propanoyl, butanoyl, pentanoyl, hexanoyl, octanoyl, dode- canoyl, tetradecanoyl, octadecanoyl, cyclohexylcarbonyl, benzoyl, methylbenzoyl, phenylacetyl, pyridylcarbonyl, naphthylcarbonyl. Some examples of substituted acyl are groups of the formula RQ9-C(O)-, where R ₀₉ is hydroxymethyl, methoxymethyl, ethoxy- methyl, 2-hydroxyeth-l-yl, 2-methoxyeth-l-yl, hydroxypropanoyl, fluoromethyl, chloro- methyl, difiuoromethyl, dichloromethyl, trifluoromethyl, trichloromethyl, aminomethyl, me- thylaminomethyl, dimethylaminomethyl, 1-aminoeth-l-yl, 1-methylaminoeth-l-yl, 1- dimethylaminoeth-1-yl, 2-aminoeth-l-yl, 3-aminoprop-l-yl, 4-aminobut-l-yl, pyrrolinyl-N- methyl, piperidinyl-N-methyl, morpholino-N-methyl, 4-amino-cyclohex-l-yl, methoxy- phenyl, hydroxyphenyl, aminophenyl, dimethylaminophenyl, hydroxybenzyl, p- aminobenzyl and p-dimethylaminobenzyl. An alkyl group Roe has from 1 to 12 carbon atoms, particularly preferably from 1 to 8 carbon atoms. The alkyl can be linear or branched. A cycloalkyl group Roe is preferably cy- dopentyl or cyclohexyl. An aryl group R ₀₆ can be naphthyl or in particular phenyl. An aral- kyl group R ₀₆ can be phenylethyl or in particular benzyl. Some examples of R ₀₆ are methyl, ethyl, n- or /-propyl, n-, i- or Mmtyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, do- decyl, cydopentyl, cyclohexyl, methylcyclohexyl, phenyl, benzyl, methylphenyl, methylben- zyl, methoxyphenyl, dimethoxyphenyl and methoxybenzyl.

In a preferred embodiment, R ₀₇ and Ros are each, independently of one another, hydrogen, Ci-C ₄ alkyl, C ₅ -C ₆ cycloalkyl, phenyl or benzyl, or R ₀₇ and R ₀₈ together are tetramethylene, pentamethylene or 3-oxapentyl-l ,5-ene. A preferred subgroup of diphosphines Y is formed by those of the formulae

wherein

Ui, U ₂ independently are CH ₂ , O, NR ₁₈ ;

U ₃ denotes CH ₂ , CF ₂ ; U ₄ and U ₅ are independently of the other R ₁₆ or together represents a ring having from 3 to 8 ring carbon atoms, being optionally heterocyclic having from 3 to 8 ring atoms and 1 or 2 hetero atoms from the group O, S and N/NR| ₈ ; m independently for each U ₃ is 1 or 2; n is 0, 1 or 2; Ri ₆ and Rn are each independently of the other hydrogen, Ci-Cβalkyl, Ci-Cβalkoxy, halogen, phenyl, benzyl, Si(Rn) ₃ , COORH, CN, CpCoalkyn, or phenyl or benzyl having from 1 to 3 C _r C ₄ alkyl or C _r C ₄ alkoxy substituents, or R] ₆ and R _n together represents an C ₃ -Cgalkylene, alkenylene, or alkynylene bridge optionally with one or more of the carbon atoms substituted with a heteroatom preferably selected from the group con- sisting of O, S and NRβ/N, said bridge optionally being substituted with one or more substituents, e.g. selected among Ci-Ci ₂ alkyl, C ₃ -C ₈ cycloalkyl, C ₆ -C _]2 aryl or C ₃ -Ci ₂ heteroaryl having heteroatoms selected from the group consisting of O, S and N, the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by Ci-Cβalkyl, Ci-C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ cycloalkoxy, phenyl, Ci- C ₆ alkylphenyl, C _r C ₆ alkoxy phenyl or C ₃ -C ₈ heteroaryl.

RH and R ₁₅ are as previously defined;

Ri ₈ is hydrogen, Ci-Cβalkyl, phenyl, benzyl, CpC _ό alkoxy-CO-, phenyl-CO-, Ci-Cβalkyl- CO-, naphthyl-CO- or CrQalkyl-NH-CO- ;

T may be identical or different groups -P(R ₇ R ₈ ), wherein R ₇ and R ₈ are as defined previously and preferably are different or identical and each preferably represents Ci-C ₆ alkyl, C _r C ₆ alkoxy, C ₅ -C ₆ cycloalkyl, phenyl, benzyl or phenyl or benzyl having from 1 to 3 Q- Cβalkyl, d-Cβalkoxy, -CF ₃ or partially or fully fluorinated CpCβalkoxy substituents; or R ₇ and Rg may form a 4 - 8 member ring such as an alkylene bridge having from 4 to 8 carbon atoms optionally with one or more of the carbon atoms substituted with a heteroatom preferably selected from the group consisting of O, S and NR ₆ ZN, said bridge optionally being substituted with one or more substituents, e.g. selected among Ci-C^alkyl, C ₃ -C ₈ cycloalkyl, Co-C^aryl or Cs-Cπheteroaryl having heteroatoms preferably selected from the group consisting of O, S and N, the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by Ci-Cβalkyl, Ci-Cβalkoxy, C ₃ - Cgcycloalkyl, C ₃ -Cgcycloalkoxy, phenyl, Ci-Cβalkylphenyl, CpCβalkoxy phenyl or C ₃ - Cgheteroaryl Of those diphosphines, chirally substituted compounds are especially preferred. Some preferred examples of diphosphines Y are as follows (Ph is phenyl):

R ₁ =Ph or cyclohexyl optionally U ₁ =O, CH ₂ substituted with 1 to 3 methyl, -CF ₃ U ₂ =O, CH ₂ , N-C _r C _θ alkyl or methoxy substituents Rk =Ph or cyclohexyl optionally R ₁ =H ₁ F, (C ₁ -C ₆ )Si, COO-C _r C _e alkyl, R, substituted with 1 to 3 methyl, -CF ₃ or methoxy substituents

Suitable diphosphines and diphosphinites have been described, for example, by H. B. Kagan in Chiral Ligands for Asymmetrie Catalysis, Asymmetrie Synthesis, Volume 5, pp. 13-23, Academic Press, Inc., N. Y. (1985). The preparation of ferrocenyl diphosphine ligands is described, for example, in United States patents nos. US 5,463,097; US 5,565,594; US 5,583,241 ; US 5,563,309; US 5,627,293; US 6,015,919; US 6,169,192; US 6,191,284, US 6,515,183; US 6,777,567; US 6,828,271 ; US 7,375,241 ; and International patent applications nos. WO 2001/04131-Al ; WO 2005/108409-A2; WO 2006/003194-A 1 ; WO 2006/003195-Al ; WO 2006/003196-Al; WO 2006/1 14438-A2; WO 2006/1 17369-A1 ; WO 2007/017522-A2 and WO 2007/020221-A2.

A ^" can be derived from inorganic or organic oxy acids. Examples include those wherein A is the anion of an organic oxy acid that contains a group C(=O)O, S(=O)O or P(=O)O in the anion. The organic oxy acid may be mono- or poly-basic, for example mono- or di-basic. Monobasic acids are especially preferred; in the case of polybasic acids, the excess acidic OH groups may be blocked, for example by esterification. The organic oxy acid may be, for example, a partial ester of an at least dibasic inorganic oxy acid, preferably those of formula Ri _O o-OSO ₂ -OH or (Ri _0O -O) ₂ P(O)-OH wherein Rioo is the monovalent radical of an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, aromatic or araliphatic alcohol having from 1 to 20 carbon atoms, preferably from 1 to 12 carbon atoms and especially from 1 to 8 carbon at- oms. Rioo may be, for example, branched and, preferably, linear Ci. ₂ oalkyl, preferably Cj. i ₂ alkyl and especially Ci.galkyl. Some examples are methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, decyl and dodecyl. R) _O o may be, for example, C ₃ . ₈ cycloalkyl and preferably C ₅ . ₆ cycloalkyl. Some examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohep- tyl and cyclooctyl. Rioo may be, for example, C ₃ .gcycloalkyl-(CH ₂ ) _P - and preferably C ₅ . ₆ cycloalkyl-(CH ₂ ) _p -, wherein p is a number from 1 to 4 and is preferably 1 or 2. Some examples are cyclopropyl-CH ₂ -, cyclobutyl-CH ₂ -, cyclopentyl-CH ₂ -, cyclohexyl-CH ₂ -, cyclo- heptyl-CH ₂ -, cyclooctyl-CH ₂ -, cyclopropyl-CH ₂ -CH ₂ -, cyclobutyl-CH ₂ -CH ₂ -, cyclopentyl- CH ₂ -CH ₂ -, cyclohexyl-CH ₂ -CH ₂ -, cycloheptyl-CH ₂ -CH _r , cyclooctyl-CH ₂ -CH _r . R, _O o may be, for example, C ₆ -i ₆ aryl, preferably C _6- ioaryl and especially phenyl. R] _0O may be, for example, optionally substituted C ₆ -C ₂ oarylene e.g. C ₆ -i ₆ aryl-(CH ₂ ) _p -, preferably Cβ-ioaryl- (CH ₂ ) _P - and especially phenyl-(CH ₂ ) _p -, wherein p is a number from 1 to 4 and is preferably 1 or 2. Some examples are benzyl, phenylethyl and naphthylmethyl.

The organic oxy acid from which A ^" is derived is preferably of formula RiorS(0) _k -OH; R,oi-( Ri ₀₀ O)iP(O)-OH or Ri ₀₂ -C(O)-OH wherein k is 1 or 2, 1 is 0 or 1, Rioo is the monovalent radical of an aliphatic, cycloaliphatic, cycloaliphatic- aliphatic, aromatic or araliphatic alcohol having from 1 to 20 carbon atoms, preferably from 1 to 12 carbon atoms and especially from 1 to 8 carbon atoms; Rioi is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, aromatic or araliphatic radical having from 1 to 20 carbon atoms, preferably from 1 to 12 carbon atoms and especially from 1 to 8 carbon atoms, that is unsubstituted or mono- or poly-substituted by C^alkyl, C|. ₆ hydroxyalkyl, Ci-βhaloalkyl (especially fluoro- or chloro-alkyl), C ₅ . ₆ cycloalkyl, C ₆ .i ₀ aryl, -OH, -F, -Cl, -Br, -CN, -NO ₂ or by -C(O)O-Ci. ₆ alkyl, it being possible for the substituents cycloalkyl and aryl to be substituted by Ci. ₆ alkyl, C,. ₆ alkoxy, -OH, -F, -Cl, -Br, -CN, -NO ₂ , Ci _-6 haloalkyl or by -C(O)O-C _i-6 alkyl; and R] ₀₂ is hydrogen or has independently the same meaning as given for R _10I . For R _]O o, the examples and preferences mentioned hereinbefore apply. Rioi and Rio ₂ may be, for example, branched and, preferably, linear Ci _-2O alkyl, preferably Ci.i ₂ alkyl and especially Ci _-8 alkyl. Some examples are methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, decyl and dodecyl. Rioi and Ri ₀₂ may be, for example, C ₃ .gcycloalkyl and preferably Cs^-cycloalkyl. Some examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. R _10I and Rio ₂ may be, for example, C ₃ .gcycloalkyl-(CH ₂ ) _P - and preferably C5-6-cycloalkyl- (CH ₂ ) _P -, wherein p is a number from 1 to 4 and is preferably 1 or 2. Some examples are cyclopropyl-CH ₂ -, cyclobutyl-CH ₂ -, cyclopentyl-CH ₂ -, cyclohexyl-CH ₂ -, cycloheptyl-CH ₂ -, cyclooctyl-CHr, cyclopropyl-CH ₂ -CH ₂ -, cyclobutyl-CH ₂ -CH _r , cyclopentyl-CH ₂ -CH ₂ -, cyclohexyl-CH ₂ -CH ₂ -, cycloheptyl-CH ₂ -CH ₂ - and cyclooctyl-CH ₂ -CH ₂ -. R _10I and Ri ₀₂ may be, for example, C ₆ -i ₆ aryl, preferably C ₆ -io aryl and especially phenyl. Rioi and Ri ₀₂ may be, for example, optionally substituted C ₆ -C ₂₀ arylene e.g. C ₆ -i ₆ aryl-(CH ₂ ) _p -, preferably Ce. ιoaryl-(CH ₂ ) _p - and especially phenyl-(CH ₂ ) _p -, wherein p is a number from 1 to 4 and is preferably 1 or 2. Some examples are benzyl, phenylethyl and naphthylmethyl.

In a preferred form, the organic acids from which A ^" is derived are of formulae Ri _0I -S(O) ₂ - OH and Ri _O i-C(O)-OH wherein R _10I is unsubstituted or Ci^alkyl, C _M alkoxy, -OH, -F, -Cl-, -Br, -NO ₂ , -C(O)O-C _1-4 alkyl, cyclopentyl-, cyclohexyl- or phenyl- substituted Ci. ₆ alkyl, preferably Ci^alkyl, Cs^-cycloalkyl or phenyl, it being possible for the substituents cyclopentyl, cyclohexyl or phenyl to be substituted by Ci^alkyl, C _]-4 alkoxy, -F, -Cl, -Br or by Ci _-4 haloalkyl. Some examples of preferred organic acids are acetic acid, propionic acid, butyric acid, mono-, di- or tri-chloro- or mono-, di- or tri-fluoro-acetic acid, perfluoropropionic acid, cyclohexanecarboxylic acid, benzoic acid, mono-, di- or tri-methylbenzoic acid, fluoro- or chloro-benzoic acid, trifluoromethylbenzoic acid, phenylacetic acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, mono-, di- or tri-chloro- or mono-, di- or tri-fluoro-methanesulfonic acid, benzenesulfonic acid, mono-, di- or tri- methylbenzenesulfonic acid and fluoro- or chloro-benzenesulfonic acid.

Complex acids from which A ^" can be derived are, for example, the halo complex acids of the elements B, P, As, Sb and Bi.

A ^" in formula (IVa) can be derived from inorganic or organic oxy acids. Examples of such acids are H ₂ SO ₄ , HClO ₄ , HClO ₃ , HBrO ₄ , HIO ₄ , HNO ₃ , H ₃ PO ₃ , H ₃ PO ₄ , CF ₃ SO ₃ H, C ₆ H ₅ SO ₃ H, CF ₃ COOH and CCl ₃ COOH. Preferred examples of A ^" derived from complex acids in formula (IVa) are ClO ₄ ^" , CF ₃ SO ₃ ^" , BF ₄ ^" , B(phenyl) ₄ \ PF ₆ ^" , SbCl ₆ ^" , AsF ₆ ^" and SbF ₆ ^" .

M ⁺ in formula (IVb) when a phosphonium cation, it may be, for example R _w R _x R _y R _z P ⁺ , wherein R _w , R _x , R _y , R _z independently of one another can be hydrogen, halogen, linear or branched C _r C ₆ alkyl, C ₃ -Ci ₂ -cycloalkyl, substituted or unsubstituted C ₆ -C _]2 aryl, substituted or unsubstituted C ₄ -Ci ₂ heteroaryl. Two of R _w , R _x , R _y , R _z can build a ring. R _w , R _x , R _y , R _z can also contain a polycyclic structure, like for example adamantyl substituents. R _w , R _x , R _y , R _z independently from each one can contain at least one chiral centre or they can be different and the chirality resides in the phosphorous atom, which can then be used as single enanti- omer or as a mixture of enantiomers. When M ⁺ is an alkali metal cation, it may be, for example, a Li, Na, K, Rb or a Cs cation. When M ⁺ is quaternary ammonium, it may be, for example R' _w R' _x R' _y R' _z N ⁺ , and it may contain a total of from 1 to 40, preferably from 4 to 24, carbon atoms. R' _w , R' _x , R' _y , R' _z independently of one another can be hydrogen, linear or branched C _r C ₆ alkyl, C ₃ -Ci ₂ cycloalkyl, substituted or unsubstituted C ₆ -Ci ₂ aryl, substituted or unsubstituted C ₄ -C _]2 heteroaryl. Two of R' _w , R' _x , R' _y , R' _z can build a ring. R' _w , R' _x , R'y, R' _z can also contain a polycyclic structure. M ⁺ may correspond to the formulae phenyl- N ⁺ (C _r C ₆ alkyl) ₃ , benzyl-N ⁺ (C,-C ₆ alkyl) ₃ or (C _r C ₆ alkyl) ₄ N ⁺ . Preferably M ⁺ is Li ⁺ , Na ⁺ or K ⁺ or (C,-C ₆ alkyl) ₄ N ⁺ . Z in formula (IV) is preferably Br or Cl and especially Cl. Z in formula (IVb), (IVe), (IVf) and (IVg) is preferably Br or I and Z in formulae (IVc) and (IVd) is preferably I.

Especially suitable diphosphine ligands which can preferably be used in iridium based catalysts of formula (IV) are, for example: {(R)-l-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dim ethyl-4-N,N-dipropyl- aminophenyOphosphine

{(R)-l-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5- diisopropyl-4-N,N-dimethyl- aminophenyl)phosphine

((R)-I -[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5-diisoprop yl-4-N,N-dibenzylyl- aminophenyl)phosphine

{(R)-l-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5- dimethyl-4-N,N-dibenzylyl- aminophenyl)phosphine

{(R)-l-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5- dimethyl-4-(l'-pyrrolo)- phenyl)phosphine {(R)-l-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dim ethyl-4-N,N-dipentyl- amino- phenyl)phosphine

{(R)-l-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5- dimethyl-4-N,N-dimethyl- aminophenyOphosphine l,4-bis(diphenylphosphino)butane

{(R)-l-[(S)-2-di(4-methoxyphenyl)phosphino)ferrocenyl]}et hyl-di(3,5-dimethyl-4-N,N- dimethylaminophenyOphosphine

{(R)-l-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5- dimethyl-phenyl)phosphine - also referred to as xyliphos

Compounds comprising a carbon-halogen bond suitable used as co-catalysts in a process according to the present invention may be selected among those compounds of formula (VI)

-C- -Hal (VI) Q ₂ wherein Hal represents a halogen atom; and Qi, Q ₂ , and Q ₃ are each independently of the other a group selected among H, linear or branched CpC^alkyl, C ₂ -Ci ₂ alkenyl or C ₂ - Ci ₂ alkynyl, C ₃ -C ₈ cycloalkyl, heterocycloalkyl bonded via a carbon atom and having from 3 to 8 ring atoms and 1 , 2 or 3 hetero atoms preferably selected from the group consisting of O, S and NRi ₉ ; or is a group selected among C ₇ -Ci ₆ aralkyl bonded via an alkyl carbon atom, Ci-Ci ₂ alkyl substituted by the mentioned C ₃ -C ₈ cycloalkyl, heterocycloalkyl or C ₃ - Cnheteroaryl bonded via a ring carbon atom and having 1, 2 or 3 hetero atoms in the ring selected from the group consisting of O, S and N/NR ₁₉ ; or is a group selected among Ce- Cπaryl, or C ₃ -Cπheteroaryl bonded via a ring carbon atom and having 1, 2 or 3 hetero atoms in the ring preferably selected from the group consisting of O, S and N; the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. -CN, -NO ₂ , F, Cl, Br, I, C _r Ci ₂ alkyl, C _r Ci ₂ alkoxy, C _r Ci ₂ alkylthio, C _r C _]2 haloalkyl, -OH, C ₆ -C _]2 aryl or -aryloxy or -arylthio, C ₇ -Ci ₆ aralkyl or -aralkoxy or - aralkylthio, secondary amino having from 2 to 24 carbon atoms, -CONRi ₉ R ₂₀ or by - COORi ₉ ; or

Q ₂ and Q ₃ together represents a group =0, =S, =NR ₁₉ =CQ ₂ Q ₃ where Q ₂ and R _]9 are as previously defined _i or Qi ₁ Q ₂ and Q ₃ together represents a group ≡CQi where Ql is as previously defined; or

Qi, Q ₂ , and Q ₃ together form, with the carbon atom to which they are attached, a ring having from 3 to 16 ring carbon atoms, being optionally heterocyclic having from 3 to 16 ring atoms and 1 , 2 or 3 (or more) hetero atoms preferably selected from the group consisting of O, S and N/NR ₁₉ , said ring optionally being substituted e.g. with -CN, -NO ₂ , halogen, Cp Ci ₂ alkyl, Ci-C ₎₂ alkoxy, C _r C ₁₂ alkylthio, C _r C _!2 haloalkyl, -OH, C ₆ -Ci ₂ aryl or -aryloxy or - arylthio, C ₇ -Ci ₆ aralkyl or -aralkoxy or -aralkylthio, secondary amino having from 2 to 24 carbon atoms, -CONR] ₉ R ₂₀ or by -COOR] ₉ ; or

Ri ₉ and R ₂₀ are each independently of the other hydrogen, CpCπalkyl, phenyl or benzyl.

Compounds of the formula (VI) may comprise additional halogen substituents identical or different from Hal.

When Qi, Q ₂ , and Q ₃ together form, with the carbon atom to which they are attached, a ring such ring may comprise one or more double bonds and may also be aromatic or heteroaro- matic and in either case include bi- or tri-cyclic structures. Preferably Qi, Q ₂ , and Q ₃ together with the carbon atom to which they are attached form a phenyl ring, being optionally heterocyclic having 1 , 2 or 3 hetero atoms, optionally being substituted by one or more substituents, e.g. -CN, -NO ₂ , halogen, C _r Ci ₂ alkyl, C _r Ci ₂ alkoxy, C,-Ci ₂ alkylthio, C,- Ci ₂ haloalkyl, -OH, C ₆ -Ci ₂ -aryl or -aryloxy or -arylthio, C ₇ -Ci ₆ -aralkyl or -aralkoxy or - aralkylthio, secondary amino having from 2 to 24 carbon atoms, -CONRi ₉ R ₂₀ or by - COORi ₉ .

Examples of substituents as mentioned above are as already described herein for R ₁ , R ₂ and R ₃ -

Preferably Hal represents I, Cl or Br, most preferably I or Br; Q ₁ represents linear or branched or C ₂ -Ci ₂ alkenyl, C ₆ -Ci ₂ aryl or C ₃ -Ci iheteroaryl bonded via a ring carbon atom and having 1, 2 or 3 hetero atoms in the ring, or C ₇ -C ₁₆ aralkyl bonded via an alkyl carbon atom; Q ₂ represents hydrogen or linear or branched C]-C ₁₂ alkyl; Q ₃ represents hydrogen or linear or branched C)-Ci ₂ alkyl; the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents; or Q ₂ and Q ₃ to- gether represents a group O or =CQ ₂ Q ₃ ; or Q _h Q ₂ , and Q ₃ together form, with the carbon atom to which they are bonded, a benzene ring, being optionally heterocyclic having 1, 2 or 3 hetero atoms, and optionally being substituted with one or more substituents such as halogen or CrCβalkyl.

Some preferred examples of compounds of the formula (VI) include, halo-benzene (e.g. iodo benzene or bromo benzene), halo-benzyl (e.g halo benzyl caring up to 5 substituents and including benzyl iodide, benzyl bromide, 2-bromo-benzylbromide, 2,3,4,5,6- Pentafluorobenzylbromide), halo-alkyl (e.g linear or branched halo-alkyl compounds such as halo-butyl compounds optionally carrying one or more substituents e.g. 1-Cl-butane or t- butylchloride, /-butylchloride or 1 ,2-dibromo-butane), halo allyl compounds such as allyl- bromide.

The employed co-catalyst compound(s) comprising a carbon-halogen bond, preferably being selected among chlorides, bromides and iodides, are used preferably in amounts of from 0.0001-10 mol%, preferably from 0.001-5 mol%, more preferably from 0.001-1 mol% and even more preferably from 0.01-1 mol%, based on the imine to be hydrogenated. The hydrogenation process is carried out as to employ the co-catalyst compound(s) in a catalytic effective amount. By catalytic effective amount is understood an amount whereby the hydrogenation reaction rate and/or turnover number of the iridium based catalyst is increased. Preferably this enhancement of reaction rate and/or turnover is 10% or more, more preferably 20% or more, even more preferably 30% or more or most preferably 40% or more compared to a similar reaction under the same conditions but without a co-catalyst being present.

Thus, an aspect of the present invention relates to a process for hydrogenating a prochiral ketimine in the presence of an effective amount of at least one chiral iridium catalyst and at least one co-catalysts comprising a carbon-halogen bond, the co-catalyst being present in an amount such that a hydrogenation reaction rate and/or turnover number of the chiral iridium catalyst is increased by 10% or more (e.g. as stated above) compared to a similar reaction under same conditions but without the co-catalyst being present, to produce an optical iso- mer of an amine having an enantiomeric excess higher than 50%, preferably higher than 70% and even more preferably higher than 80%.

Compounds of the formula (VI) are readily available or may be produced according to well known methods.

The process according to the invention may comprise the use of an additional co-catalyst se- lected among phosphonium halide, metal halide or ammonium halides, the halides preferably selected among chlorides, bromides and iodides. Phosphonium is preferably trialkyl phosphonium halides having from 1 to 40 carbon atoms in the alkyl groups. Special preference is given to diadamantylbutylphosphonium iodide or diadamantylbenzylphosphonium bromide or triphenylisopropylphosphonium iodide or triphenylmethylphosphonium bromide. Other preferred phosphonium salts are triphenylmethylphosphonium bromide, diphenyl iso- propyl phosphonium iodide, and triphenyl isopropyl phosphonium iodide. Metal halides include LiCl, LiBr, LiI, NaI, or NaBr. Examples of ammonium halides are tetraalkylammo- nium halides having 1 to 6 carbon atoms in the alkyl groups and include tetrabutylammo- nium iodide. In a preferred embodiment of the present invention, the process is carried out without the addition of any phosphonium-, metal- and/or ammonium-halides.

The reaction can be carried out in the absence or in the presence of inert solvents. Suitable solvents, which can be used alone or as a mixture of solvents, are especially aprotic solvents.

The process according to the invention can be performed without adding an acid. However, it further embraces optionally the additional use of an acid. It may be an inorganic or, preferably, an organic acid. When present, the acid is preferably used in at least the same molar amount as the iridium catalyst (equivalent to catalytic amounts) and can also be used in excess. The excess may even consist in the use of the acid as solvent. Preferably the acid is used from 0.001 to 50%, in particular from 0.1 to 50% by weight, based on the substrate to be hydrogenated. In many cases it can be advantageous to use anhydrous acids.

Some examples of inorganic acids are H ₂ SO ₄ , highly concentrated sulfuric acid (oleum), H ₃ PO ₄ , orthophosphoric acid, HF, ^' HCl, HBr, HI, HClO ₄ , HBF ₄ , HPF ₆ , HAsF ₆ , HSbCl ₆ , HSbF ₆ and HB(phenyl) ₄ . H ₂ SO ₄ is particularly preferred. Examples of organic acids are aliphatic or aromatic, optionally halogenated (fluorinated or chlorinated) carboxylic acids, sulfonic acids, phosphorus(V) acids (for example phosphonic acids, phosphonous acids) having preferably from 1 to 20, especially from 1 to 12 and more especially from 1 to 6, carbon atoms. The organic acid can also contain at least one chiral center, like tartaric acid or camphorsulfonic acid. Other examples of organic acids are formic acid, acetic acid, propionic acid, butyric acid, benzoic acid, phenylacetic acid, cyclo- hexanecarboxylic acid, chloro- or fluoro-acetic acid, dichloro- or difluoro-acetic acid, tri- chloro- or trifluoro-acetic acid, chlorobenzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, chlorobenzenesulfonic acid, trifluoro- methanesulfonic acid, methyl-phosphonic acid and phenylphosphonic acid. Preferred acids are acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid and chloroacetic acid.

It is also possible for acidic ion exchangers of an inorganic or organic nature to be used as the acids, or metal oxides in gel form, like for example Siθ ₂ , Geθ ₂ , B ₂ O ₃ , AI ₂ O ₃ , TiO ₂ , Zrθ ₂ and combinations thereof.

In a preferred embodiment of the present invention, the process is carried out without the addition of an acid.

The preparation of the catalysts is known per se and is described for example in such previous references found herein. The preparation of the catalysts of formula (IV) can be carried out, for example, by reacting a di-iridium complex of the formula [XIrZ] ₂ (with X, and Z being as defined herein previously) with a diphosphine, e.g. a diphosphine Y as defined herein. The iridium catalysts can be added to the reaction mixture as isolated compounds. It has proved advantageous, however, to produce the catalyst in situ with or without an inert solvent prior to the reaction and to add the co-catalyst compound comprising a carbon- halogen bond and eventually a portion or all of the optional acid present in the hydrogena- tion reaction media.

The iridium based catalysts are preferably used in amounts of from 0.0001 to 10 mol%, especially from 0.0005 to 10 mol%, and more especially from 0.001 to 10 mol%, based on the imine. The process is carried out preferably at a temperature of from -20 to 100 ⁰ C, especially from 0 to 8O ⁰ C and more especially from 10 to 7O ⁰ C, and preferably at a hydrogen pressure of 2 x 10 ⁵ to 1.5 x 10 ⁷ Pa (2 to 150 bar), especially 10 ⁶ to 10 ⁷ Pa (10 to 100 bar).

In detail, the process according to the invention can be carried out by first preparing the catalyst by dissolving, for example, (Ir-dieneCl) ₂ in a inert solvent, adding a diphosphine and stirring the mixture and optionally adding further reagents such as additional co- catalysts that may have a positive effect on the desired catalytic properties and selectivity. (Ir-dieneCl) ₂ can also be used in solid form. A compound comprising a carbon-halogen bond and optionally an acid is added to a solution of imine in an autoclave and the above catalyst solution is added (or vice versa). Hydrogen pressure is applied, thus removing the protective gas that is advantageously used. It is advantageous to ensure that the catalyst solution stands for only a short time, and to carry out the hydrogenation of the imines as soon as possible after the preparation of the catalyst. The reaction mixture is heated, if desired, and then hydrogenated. Where appropriate, when the reaction has ceased the reaction mixture is cooled and the autoclave is depressurized. The reaction mixture can be removed from the autoclave under pressure with nitrogen and the hydrogenated organic compound can be isolated and purified in a manner known per se, for example by extraction or distillation.

In the case of the hydrogenation of aldimines and ketimines, the aldimines and ketimines can also be formed in situ before or during the hydrogenation. In a preferred form, an amine and an aldehyde or a ketone are mixed together and added to the catalyst solution and the aldimine or ketimine formed in situ is hydrogenated. It is also possible, however, to use an amine, a ketone or an aldehyde together with the catalyst as the initial batch and to add the ketone or the aldehyde or the amine thereto, either all at once or in metered amounts. The hydrogenation can be carried out continuously or batchwise in various types of reactors. Preference is given to those reactors which allow comparatively good intermixing and good removal of heat, such as for example, loop reactors. That type of reactor has proved to be especially satisfactory when small amounts of catalyst are used.

The process according to the invention yields the corresponding amines in short reaction times while having chemically a high degree of conversion, with surprisingly good optical yields (ee) of 50% or more being obtained even at relatively high temperatures of more than 5O ⁰ C.

The hydrogenated organic compounds that can be prepared in accordance with the invention, for example the amines, are biologically active substances or are intermediates for the preparation of such substances, especially in the field of the preparation of pharmaceuticals and agrochemicals. For example, 0,0-dialkylarylketamine derivatives, especially those having alkyl and/or alkoxyalkyl groups, are effective as pesticides, especially as herbicides. The derivatives may be amine salts, acid amides, for example of chloroacetic acid, tertiary amines and ammonium salts. Especially important in this connection are the optically active amines of formula (Ha), (lib) and (lie)

(Ha) (lib) (lie) which can be prepared from the imines of formula (Ia), (Ib) and (Ic) respectively using the hydrogenation processes as disclosed herein, and which can be converted in accordance with methods that are customary per se with chloroacetic acid into the herbicides of the chloroacetanilide type.

The above symbol * indicates predominantly one configurational isomer, which means that the enantiomeric excess (ee) is at least 50%, preferably at least 70% and particularly pref- erably at least 80%.

Thus, the present invention further relates to a process for the preparation of a compound of either formula (Ilia), (UIb) or (IIIc)

comprising the steps of i. forming a reaction mixture comprising a) an imine compound of either formula (Ia), (Ib) or (Ic) respectively and optionally an inert solvent, and b) one or more iridium complexes as catalysts, preferably iridium complexes comprising compounds of the formula (VII) as ligands, and one or more co-catalysts selected among compounds comprising a carbon-halogen bond, preferably a co-catalyst selected among com- pounds of the formula (VI); ii. reacting the reaction mixture with hydrogen under elevated preassure to form an amine compound of either formulae (Ha), (lib) or (He) respectively; iii. reacting the thus formed amine with chloroacetic acid chloride. In particular the above process relates to the process for the preparation of the compound CIIIb) predominantly in its (^-configuration, this compound also known as S-Metolachlor having herbicidal properties, such process comprising hydrogenation of the imine of the formula (Ib) with hydrogen under elevated pressure in the presence of one or more iridium complexes as catalyst and one or more compounds comprising a carbon-halogen bond as co-catalysts to form the compound of formula (lib) and subsequent reaction with chloroace- tic acid chloride.

Within the group of diphosphine ligands useful according to the present invention are the novel ferrocenyl ligands of formula (VII) or formula (VIII) that have been found to show a significant effect when used as part of iridium complexes as catalysts in a process for the hydrogenation of imines with hydrogen under elevated pressure and in the presence of one or more co-catalysts selected among compounds comprising a carbon-halogen bond as described herein:

(VII) (VIII) wherein

R' π ₊₁₅ represents an C _r Cgalkylene, alkenylene, or alkynylene bridge optionally with one or more of the carbon atoms substituted with a heteroatom, said bridge optionally being substituted with one or more substituents that may be selected among C _r Ci ₂ alkyl, C ₃ - Cgcycloalkyl, C ₆ -Ci ₂ aryl or C ₃ -Ci ₂ heteroaryl having heteroatoms preferably selected from the group consisting of O, S and N; the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by Ci-Cβalkyl, Q- C ₆ alkoxy,

C ₃ -Cgcycloalkyl, C ₃ -Cgcycloalkoxy, phenyl, Ci-C ₆ alkylphenyl, Ci-C ₆ alkoxy phenyl or C ₃ - Cgheteroaryl; X ₂ represents a secondary phosphine group;

R' io and R' n are each independently of the other C _r Ci ₂ alkyl, Ci-Ci ₂ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ -Cgcycloalkoxy, C ₆ -Ci ₂ aryl, C ₃ -C _]2 heteroaryl, Cβ-Cπaryl-Ci-Cπalkyl-, Cβ-Cnaryl-Ci-Cnalkoxy- or Cs-Cnheteroaryl-Ci-Cπalkyl- having heteroatoms preferably selected from the group consisting of O, S and N, the aforementioned groups being unsub- stituted or substituted independently of the others by one or more substituents e.g. by C]- C ₆ alkyl, Ci-C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ cycloalkoxy, phenyl, phenyl-C _r C ₆ alkyl- (e.g. benzyl), phenyl-C _r C ₆ alkoxy-, C ₃ -C ₈ heteroaryl, (Ci-Ci ₂ alkyl) ₃ Si, (C ₆ -Ci ₂ aryl) ₃ Si, -NH ₂ , (phenyl) ₂ N-, (benzyl) ₂ N-, moφholinyl, piperidinyl, pyrrolidinyl, (Ci-Ci ₂ alkyl) ₂ N-, (C ₇ - Ci ₂ aralkyl) ₂ N-, C _r Ci ₂ haloalkyl, Ci-Ci ₂ haloalkoxy, halogen, -ammonium-Xi, -SO ₃ Mi, - CO ₂ M ₁ , -PO ₃ Mi or by -COO-CpC _δ alkyl, wherein M] is an alkali metal or hydrogen and Xi is the anion of a monobasic acid.

R'i ₄ represents hydrogen, OR'oo, Ci-C] ₂ alkyl, Ci-C ₄ fluoroalkyl, C ₃ -Cgcycloalkyl, C ₆ -Ci ₂ aryl or C ₃ -Ci ₂ heteroaryl having heteroatoms preferably selected from the group consisting of O, S and N.

R' is represents an alkyl group, preferably a C]-C ₂ oalkyl group, substituted by at least one group OR'oo or NRO ₇ ROs and said alkyl group may be further substituted by e.g. one or more substituents such as halogen, C]-C ₆ alkyl, C)-C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ - Cgcycloalkoxy, phenyl, C _r C ₆ alkyl phenyl, C _r C ₆ alkoxy phenyl, C ₃ -Cgheteroaryl or halogen. If more than one OR'oo and/or NR' _O7 R'os group is present then such groups may be identical or different from one another.

R'oo represents hydrogen, H, Ci-Ci ₂ alkyl, C _r C| ₂ alkenyl, Ci-C _]2 alkynyl, C ₃ -Cgcycloalkyl, C ₆ -C] ₂ aryl, R'oi RO ₂ ROsSi or Q-Cigacyl that is optionally substituted, e.g. by halogen, hydroxy, CpCsalkoxy or RO4RO ₅ N-; R'oi, R' ₀₂ and RO ₃ are each, independ- ently of one another, Ci-C] ₂ -alkyl, unsubstituted or Ci-C ₄ alkyl or Ci-C ₄ alkoxy-substituted C ₆ -Ci ₀ aryl or C ₇ -C] ₂ aralkyl; R' _O4 and R' ₀₅ are each, independently of one another, hydrogen, Ci-C _t2 alkyl, C ₃ -C ₈ cycloalkyl, C ₆ -Ci ₀ aryl or C ₇ -Ci ₂ -aralkyl, or R' ₀₄ and R' ₀₅ together are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by halogen, Ci-Cβalkyl, Ci-Cβalkoxy, C ₃ -Cgcycloalkyl, C ₃ -Cgcycloalkoxy, phenyl, Cp C ₆ alkyl phenyl, Ci-Cβalkoxy phenyl, C ₃ -Cgheteroaryl; R' _O7 and R' _O8 independently of one another represents hydrogen, C _r Ci ₂ alkyl, C ₃ -C ₈ cycloalkyl, C ₆ -Ci ₀ aryl or C ₇ -Ci ₂ -aralkyl, or R' _O7 and R' _O g together are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by halogen, CpQalkyl, C _r C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ - Cgcycloalkoxy, phenyl, Ci-C ₆ alkyl phenyl, Ci-C ₆ alkoxy phenyl, C ₃ -C ₈ heteroaryl.

In a preferred embodiment R'oo represents hydrogen, Ci-C ₆ alkyl or R'oiR'o ₂ R'o ₃ Si. Preferably R' _{1 1+15} represents an optionally substituted C ₃ -C ₆ alkylene bridge and more pref- erably an optionally substituted C ₃ -C ₅ alkylene bridge.

In a preferred embodiment X ₂ represents the group R' ₇ R'gP wherein R' ₇ and R'g independently of the other are as defined for R' _1O .

Preferably R' ₇₎ R' ₈ , R' ₎₀ and R'π each independently of the others represent CpCnalkyl, CpC^alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ -Cgcycloalkoxy, C ₆ -Ci ₂ aryl C ₃ -Ci ₂ heteroaryl, C ₆ -Ci ₂ aryl-Ci-Ci ₂ alkyl-, C ₆ -Ci ₂ aryl-Ci-Ci ₂ alkoxy- or C ₃ -Ci ₂ heteroaryl-Ci-C] ₂ alkyl- having heteroatoms preferably selected from the group consisting of O, S and N; the aforementioned groups being unsubstituted or substituted independently of the others by one or more substituents e.g. by one or more groups selected among Ci-C ₆ alkyl, C|-C ₆ alkoxy, C ₃ - Cgcycloalkyl, C ₃ -C ₈ cycloalkoxy, phenyl, phenyl-Ci-C ₆ alkyl-, phenyl-Q-Cealkoxy-, C ₃ - Cgheteroaryl, (C _r C ₁₂ alkyl) ₃ Si, (C ₆ -C ₁₂ aryl) ₃ Si, -NH ₂ , (phenyl) ₂ N-, (benzyl) ₂ N-, mor- pholinyl, piperidinyl, pyrrolidinyl, (Ci-Ci ₂ alkyl) ₂ N-, (C ₇ -C _]2 aralky I) ₂ N-, Ci-C _{] 2} haloalkyl, Ci-Ci ₂ haloalkoxy or halogen; or R' ₇ and R'g together represents an alkylene bridge having from 2 to 6 carbon atoms that is optionally interrupted by 1 or more -O-, -S- or -N- compris- ing radicals such as N-H, N-Ci-C^alkyl or N-C ₆ -Ci ₂ aryl; and may be unsubstituted or substituted by =O or by one or more groups of Ci-C ₆ alkyl, Ci-C ₆ alkoxy, C ₃ -C ₈ cycloalkyl, C ₃ - Cgcycloalkoxy, phenyl, phenyl-CpCβalkyl-, phenyl-Ci-C ₆ alkoxy-, or halogen groups; and/or condensed with benzene, pyridine, pyrimidine, furan, thiophene or pyrrole.

R' ₇ , R'g, R' ₁₀ and R' π can be substituted in any positions by identical or different radicals, for example by from 1 to 5, preferably from 1 to 3, substituents

More preferably R' ₇ , R'g, R' _1O and R'π each independently of the others represent Cp Cβalkyl; GrC _ό Cycloalkyl that are unsubstituted or have from 1 to 3 Ci-C ₄ alkyl or Ci-C ₄ alkoxy substituents; phenyl or benzyl that is unsubstituted or has from 1 to 3 C _r C ₄ alkyl, Ci-C ₄ alkoxy, F, Cl, Ci-C ₄ fluoroalkyl or Ci-C ₄ fluoroalkoxy substituents. R' i ₄ preferably represent hydrogen.

R' ₁₅ is preferably a Ci-C ₆ alkyl group substituted by at least one group OR'oo or NRO ₇ ROs _, and more preferably substituted by OR'oo _, preferably just one OR'oo group, wherein R' _O o preferably represents H, Ci-Qalkyl or ROiRO ₂ ROsSi. Most preferably R' ₁₅ is a C ₂ -Csalkyl group substituted by one OR'oo group wherein R'oo preferably represents H, C _r C ₃ alkyl or

R'oi. R' ₀₂ , R'o ₃ independently of one another preferably represents linear or branched Cp Cg-alkyl, phenyl or benzyl optionally being substituted by one or more substituents e.g. by one or more C _r C ₄ alkyl, C _r C ₄ haloalkyl or C _r C ₄ alkoxy groups. The OR'oo group is preferably terminal positioned.

The cyclopentadienyl moiety of the ferrocenyl groups in the above formula (VII) or formula (VIII) may be substituted independently of one another, e.g. by one or more substituents that may the same or different e.g. halogen or a substituent bonded via a C atom, N, atom, S atom, Si atom, a P(O) group or a P(S) group. Such groups may include any of the following that may be further substituted: methyl, ethyl, n- and /-propyl, n-, i- and ?-butyl, pentyl, hexyl, cyclohexyl, cyclohexyl methyl, phenyl, benzyl, trimethylsilyl, F, Cl, Br, methylthio, methylsulphonyl, methylsulphoxyl, phenylthio, phenylsulphonyl, phenylsulphoxyl, -CH(O), -C(O)OH, -C(O)-OCH ₃ , -C(O)-OC ₂ H ₅ , -C(O)-NH ₂ , -C(O)-NHCH ₃ , -C(O)-N(CH ₃ ) ₂ , -SO ₃ H, -S(O)-OCH ₃ , -S(O)-OC ₂ H ₅ , -S(O) ₂ -OCH ₃ , -S(O) ₂ -OC ₂ H ₅ , -S(O)-NH ₂ , -S(O)-NHCH ₃ , - S(O)-N(CHj) ₂ , -S(O)-NH ₂ , -S(O) ₂ -NHCH ₃ , -S(O) ₂ -N(CH ₃ ) ₂ , -P(OH) ₂ , PO(OH) ₂ , - P(OCH ₃ ) ₂ , -P(OCH ₃ ) ₂ , -PO(OCH ₃ ) ₂ , -PO(OC ₂ H ₅ ) ₂ , trifluoromethyl, methylcyclohexyl, me- thylcyclohexylmethyl, methylphenyl, dimethylphenyl, methoxyphenyl, dimethoxyphenyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, -CH ₂ NH ₂ , -CH ₂ N(CH ₃ ) ₂ , -CH ₂ CH ₂ NH ₂ , - CH ₂ CH ₂ N(CH ₃ ) ₂ , methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, HS-CH ₂ -, HS-CH ₂ CH ₂ -, CH ₃ S-CH ₂ -, CH ₃ S-CH ₂ CH ₂ -, -CH ₂ -C(O)OH, -CH ₂ CH ₂ -C(O)OH, -CH ₂ - C(O)OCH ₃ , -CH ₂ CH ₂ -C(O)OCH ₃ , -CH ₂ -C(O)NH ₂ , -CH ₂ CH ₂ -C(O)NH ₂ , -CH ₂ -C(O)- N(CH ₃ ) ₂ , -CH ₂ -SO ₃ H, -CH ₂ CH ₂ -C(O)N(CH ₃ ) ₂ , -CH ₂ CH ₂ -SO ₃ H, -CH ₂ -SO ₃ CH ₃ , -CH ₂ CH ₂ - SO ₃ CH ₃ , -CH ₂ -SO ₂ NH ₂ , -CH ₂ -SO ₂ N(CH ₃ ) ₂ , -CH ₂ -PO ₃ H ₂ , -CH ₂ CH ₂ -PO ₃ H ₂ , -CH ₂ - PO(OCH ₃ ), -CH ₂ CH ₂ -PO(OCH ₃ ) ₂ , -C ₆ H ₄ -C(O)OH, -C ₆ H ₄ -C(O)OCH ₃ , -C ₆ H ₄ -S(O) ₂ OH, - C ₆ H ₄ -S(O) ₂ OCH ₃ , -CH ₂ -O-C(O)CH ₃ , -CH ₂ CH ₂ -O-C(O)CH ₃ , -CH ₂ -NH-C(O)CH ₃ , - CH ₂ CH ₂ -NH-C(O)CH ₃ , -CH ₂ -O-S(O) ₂ CH ₃ , -CH ₂ CH ₂ -O-S(O) ₂ CH ₃ , -CH ₂ -NH-S(O) ₂ CH ₃ , - CH ₂ CH ₂ -NH-S(O) ₂ CH ₃ , -P(O)(C ,-C ₈ alkyl) ₂ , -P(S)(C,-C ₈ alkyl) ₂ , -P(O)(C ₆ -C, ₀ aryl) ₂ , - P(S)(C ₆ -C ₁₀ aryl) ₂ , -C(O)-C, -C ₈ alkyl and -C(O)-C ₆ -C ₁₀ aryl. The compounds of formula (VII) or formula (VIII) may be present in the form of racemates, mixtures of diastereomers or optically pure stereoisomers. Preferably the compounds are present in enatiomeric excess of the desired isomer, for example, higher than 50%, preferably higher than 60%, more preferably higher than 70% and even more preferably higher than 85%, most preferably the desired isomer is synthesised or isolated in >99% purity rela- tive to any of the other diastereomers having the general formula (VII) or (VIII) respectively.

Compounds of the formula (VII) may be prepared according to the following general reaction scheme:

XII XIV XV

Optional protection

(Hal-)Metal-R' _1β ne

XIX XVI

1 Base R ₁₀ PH ₂ Acid 1 Deprotection

2 X ₂ -HaI 2 LG activation

XVII XXII VII

Compounds of the formula (VIII) may be prepared according to the following general reaction scheme:

XII XIV XV

Optional protection (Hal-)Metal-R' ₁₆ 1 LG activation

2 Secondary amine

XIX XX XXI XVI

vtSv R ₁ I

Amine R ₁₀ R i ₁ PH Aαd

XVII XVlIl VIII

In the above reaction scheme the substituents X ₂ , R'io, R'n, R' i _4> R' is are as defined previously. Hal represents a halogen atom, preferably Br or Cl. Metal is preferably Mg. Amine is a secondary amine, preferably an amine substituent of formula NRO ₇ RO ₈ wherein R' _O7 and R'o ₈ are as herein previously defined, and is preferably independently of one another Q- Ci ₂ alkyl, C ₃ -C ₈ cycloalkyl, C ₆ -Ci _O aryl or C ₇ -Ci ₂ -aralkyl.

When the goal is the preparation of compounds of general formula (VIII) wherein the substituent R' ₁₅ comprise at least one hydroxy group (i.e. OR'oo represents OH), it is usually necessary, but dependent on reaction conditions, to protect such group(s) during the course of the above reaction sequence e.g. with a protecting group such as a silyl group of formula R'oiR'o ₂ R-'o ₃ Si wherein R' _O i, R'0 ₂ , R'03 are as defined previously herein or an acyl group, e.g. CpCigacyl that is optionally substituted, e.g. Ci-Cgalkoxycarbonyl groups (for example /-butoxycarbonyl), Ci-Cgalkenyloxycarbonyl groups (for example allyloxycarbonyl), C ₆ - Ci ₂ aryl-Ci-C ₈ alkoxycarbonyl groups (e.g benzoyloxycarbonyl, p-ethoxybenzyloxycarbonyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl). Accordingly R'i ₆ is as defined for R' ₁₅ but when R' ₁₆ comprise a group OR'oo, R'oo further includes, besides H, silyl and acyl, other hydroxyl protection groups known in the art such as e.g. Q-Cgalkyl groups (for example tert-butyl), Q-Cgalkenyl groups (for example allyl) or C ₇ -Ci ₆ aralkyl bonded via an alkyl carbon atom (for example benzyl groups). R' ₁₇ represents an alkyl group, preferably a CpCgalkyl group. n is an integer having a value of 0 or higher, preferably an integer between 0-1 1.

Thus, in the above scheme formula (XV) compared with formula (XVI) as well as formula (XVIII) compared with formula (VIII) the difference, respectively, is the optional presence of hydroxy protection groups.

Initially, compounds of formula (XI) are obtained by acylation of ferrocene using known literature procedures (Angew. Chem. Int. Ed. 1971, 10, 191). For simultaneous insertion of a preferred central and planar chirality, the acylated ferrocene (XI) can in principle be converted by any of the methods that are possible to the skilled artisan for this reaction (e.g. J. Am. Chem. Soc. 1957, 79, 2742, J. Organometal. Chem. 1973, 52, 407-424). However, reduction with the so-called CBS reagent (J. Am. Chem. Soc. 1987, 109, 5551-5553, Tetrahedron Lett. 1996, 37, 25-28) is preferable. This procedure ensures that (XII) are produced in very good yields and with very high optical purity. Another conceivable path for preparation of the desired enantiomer-enriched ligands can take place, for example, by preparing the alkylated ferrocenes by means of enantioselective reductive amination. One equally arrives at the enantiomer-enriched ligands with an amine substituent at the stereogenic center in this manner. Other possibilities for introduction of chirality are described in principle in Tetrahedron Asymmetry 1991, 2, 601-612, J. Org. Chem. 1991, 56, 1670-1672, J. Org. Chem. 1994, 59, 7908-7909, J. Chem. Soc, Chem. Commun. 1990, 888-889. The enanti- omer-enriched alcohols (XII) that are obtained by the above described CBS reaction can now be converted to derivatives of formula (XIV) in all of the ways that are known to the skilled artisan. Preferably the derivatives are made by replacing the OH function at the stereogenic center by an amino group by forming an intermediate leaving group and subsequently substitution with a secondary amine. Compounds of the general formula (XV) are obtained by reduction of the ester functionality and optionally further elaboration of the hydroxy product to give (XVI). Alternatively (XVI) may be prepared starting from compounds of the general formula (XIX): Addition of an organometallic reagent provides (XX), which may be transformed into the racemic amine adduct (XXI), by a leaving group activation, followed by substitution with a secondary amine. The racemic intermediate may be resolved by using an optically active acid providing (XVI) as an optically enriched product (e.g. J. Am. Chem. Soc. 1970, 92, 5389-5393). Especially preferred is the preparation of dial- kylamino derivatives, since these can be employed for the further conversion to (XVII). In this step, the dialkylamino derivatives (XVII) can advantageously be deprotonated in the α position of the cyclopentadienyl ring and then reacted with an electrophile to introduce a phosphine, preferably a diarylphosphine. The deprotonation reaction can take place with all of the agents that are commonly known to the skilled artisan for this purpose, but preferred is the use of the strong bases n-butyllithium (n-BuLi), s-butyllithium (s-BuLi), or t- butyllithium (t-BuLi) in an inert solvent. Preferably the lithium resultingly bonded to ferro- cene is converted to a diarylphosphine with a phosphine reagent. Because of the chirality present in the molecule, of the two a positions in the ring, one is preferably deprotonated and substituted (J. Am. Chem. Soc. 1970, 92, 5389-5393). Preferred possibilities as phosphine reagents are compounds that have a leaving group at the phosphorus atom and thus exhibit electrophilic character. Such reagents are sufficiently well known to the skilled artisan (J. Am. Chem. Soc. 1955, 77, 3526-29). The use of diphenylphosphine chloride is preferred. Reaction of (XVII) with a primary phosphine under acidic conditions substitutes the amine of (XVII) with retention of configuration providing (XXII) as an optically enriched product (J. Org. Chem. 1972, 37, 3052-3058. Finally, (VII) may be obtained by a sequential deprotection/leaving group activation procedure facilitating ring closure of the phosphine moiety and R'i ₆ - Ferrocenyl ligands with the general formula VIII may also be prepared starting from (XVII). Reaction with a disubstituted phosphine in the presence of an acid displaces the amine of (XVII) with retention of configuration. Finally, an optional deprotection of (XVIII) provides access to (VIII).

The invention further provides complexes of metals selected among the group of transition metals of the Periodic Table with one of the compounds of the formula (VII) or formula (VIII) as ligand. Possible metals are, for example, Cu, Ag, Au, Ni, Co, Rh, Pd, Ir, Ru and Pt. Preferred metals are rhodium and iridium and also ruthenium, platinum, palladium and copper. Particularly preferred metals are ruthenium, rhodium and iridium with iridium being most preferred. The metal complexes can, depending on the oxidation number and coordination number of the metal atom, contain further ligands and/or anions. They can also be cationic metal complexes. Such analogous metal complexes and their preparation have been widely described in the literature. These metal complexes comprising ligands of the formula (VII) or formula (VIII) are preferably homogeneous catalysts or catalyst precursors which can be activated under the reaction conditions which can be used for asymmetric addition reactions onto prochiral, unsaturated, organic compounds. The complexes may also contain further ligands and/or anions. Accordingly the present invention also relates to a process for preparing chiral organic compounds by asymmetric addition of hydrogen onto a carbon- carbon or carbon-heteroatom double bond in prochiral organic compounds, wherein the addition reaction is carried out in the presence of catalytic amounts of at least one metal complex comprising ligands of the formula (VII) or formula (VIII), as well as the use of metal complexes comprising ligands of the formula (VII) or formula (VIII) as homogeneous catalysts for the preparation of chiral organic compounds, preferably for the asymmetric addi- tion of hydrogen onto a carbon-carbon or carbon-heteroatom double bond in prochiral organic compounds.

The novel metal complexes can, for example but preferably, correspond to the general formulae (IVh) or (IVi):

[L _r MeL,] (IVh) [L _n MeL ₁ ] ^(z+) (A ^" ) _z (IVi) where Li is one of the compounds of the formula (VII) or formula (VIII);

L represents identical or different monodentate, anionic or nonionic ligands, or

L represents identical or different bidentate, anionic or nonionic ligands; r is 2, 3 or 4 when L is a monodentate ligand or r is 1 or 2 when L is a bidentate ligand; z is 1, 2 or 3; Me is a metal selected from the group consisting of Rh, Ir and Ru; with the metal having the oxidation state 0, 1 , 2, 3 or 4;

A ^" is the anion of an oxy or complex acid as previously described herein; and the anionic ligands balance the charge of the oxidation state 1, 2, 3 or 4 of the metal.

Monodentate nonionic ligands can, for example, be selected from the group consisting of olefins (for example ethylene, propylene), solvating solvents (nitriles, linear or cyclic ethers, unalkylated or N-alkylated amides and lactams, amines, phosphines, alcohols, carboxylic esters, sulphonic esters), nitrogen monoxide and carbon monoxide. Suitable polydentate anionic ligands are, for example, allyls (allyl, 2-methallyl), cyclopen- tadienyl or deprotonated 1,3-diketo compounds such as acetylacetonate.

Monodentate anionic ligands can, for example, be selected from the group consisting of halogens (F, Cl, Br, I), pseudohalide (cyanide, cyanate, isocyanate) and anions of carboxylic acids, sulphonic acids and phosphonic acids (carbonate, formate, acetate, propionate, me- thylsulfonate, trifluoromethylsulphonate, phenylsufonate, tosylate).

Bidentate nonionic ligands can, for example, be selected from the group consisting of linear or cyclic diolefins (for example hexadiene, cyclooctadiene, norbornadiene), dinitriles (malononitrile), unalkylated or N-alkylated carboxylic diamides, diamines, diphosphines, diols, dicarboxylic diesters and disulphonic diesters.

Bidentate anionic ligands can, for example, be selected from the group consisting of anions of dicarboxylic acids, disulphonic acids and diphosphonic acids (for example of oxalic acid, malonic acid, succinic acid, maleic acid, methylenedisulphonic acid and methylenediphos- phonic acid). Preferred metal complexes which are particular suitable for hydrogenations are those where Me in the above formulae represents iridium or rhodium, and preferably iridium complexes corresponding to those of formula (IV) and formula (IVa) wherein Y corresponds to L ₁ as above i.e. ligands of the formula (VII) or formula (VIII).

Metal complexes comprising ligands of the formula (VII) or formula (VIII), by example complexes according to formulae (IVh) or (IVi), are prepared by known methods. Use of such metal complexes as homogenous catalysts for e.g. asymmetric hydrogenation (addition of hydrogen) of prochiral unsaturated organic compounds, e.g. compounds comprising one or more carbon-carbon or carbon-heteroatom double bonds, are generally known from the literature. The present invention also relates to novel intermediates of formulae (XVI'), (XVII') and (XXII'), which are precursors to the compounds (VII) and (VIII), and which may by themselves function as ligands useful as part of metal complexes e.g. useful as catalysts in a process for the hydrogenation of imines with hydrogen.

(XVl') (XVII ¹ ) (XXII ¹ ) wherein the substituents X ₂ , R'07, R-Os, R'io, R'u _> R' 15 are as defined previously and wherein the cyclopentadienyl rings in the above structures, independently of one another, may be substituted by one or more substituents, e.g. as described for the compounds of for- mula (VII) and formula (VIII).

The compounds of formula (XVI), formula (XVII) or formula (XXII) may be present in the form of racemates, mixtures of diastereomers or optically pure stereoisomers. Preferably the compounds are present in enatiomeric excess of the desired isomer, for example, higher than 50%, preferably higher than 60%, more preferably higher than 70% and even more preferably higher than 80%.

The invention is illustrated by the following non-limiting examples:

Example 1

(Ib) (lib) S-NAA

Catalyst preparation: To a flame-dried Schlenk flask was added [Ir(cod)Cl] ₂ (1.28 mg, 0.002 mmoles, 0.01 mol %), Xyliphos i.e. the compound {(R)-l-[(S)-2- diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-phenyl)p hosphine (2.55 mg, 0.004 mmoles, 0.02 mol %) and dry degassed THF (0.5 mL) under argon to give a yellow colored homogenous solution.

To an autoclave was added MEA-imine (Ib) (4.0 g, 19.5 mmoles, 1 eq.) and 2,3,4,5,6- pentafluorobenzyl bromide (7.2 μL, 0.05 mmoles, 0.26 mol %). The reaction vessel was sealed and purged three times with nitrogen under stirring before adding the above catalyst solution through the injector system. The injector system was washed once with dry degassed THF (0.5 mL) before purging three times with hydrogen under stirring. The reaction was initiated by heating to 5O ⁰ C and then introducing high pressure hydrogen (30 bar) to the reaction vessel. After 4 hours the reaction vessel was allowed to reach room temperature before releasing the hydrogen. GC yield: >99%. Optical purity: 75 % ee (5 configuration) - see table 1 , entry 19.<

A series of experiments using the above procedure was carried out with various parameters as seen in table 1 - entries 1 -9 for a comparative purpose.

Results for the screening of aromatic halides and alkyl halides as additives for the catalytic enantioselective hydrogenation of MEA-imine (Ib) to S-NAA (lib).

Table 1

All experiments are carried out at 50 ⁰ C and 30 bar hydrogen pressure. Entries marked with a (c) are for a comparative purpose

PFBnBr = 2,3,4,5,6-Pentafluorobenzylbromide. AcOH = Acetic acid

S/C = Substrate to catalyst ratio

Example 2

Examples of how to prepare specific ligands falling within formula (VIII) is provided e.g. via process Route A or Route B, whereas the preparation of a specific ligands falling with formula (VII) by example is provided by example in process Route C.

Route A

Route B

XVIII -I VIII-1,5,1

Route C XXIM \J

General procedure for the synthesis of VIII, Succinic anhydride approach (Route A).

a) IX-1 X-1

72 g (0,39 mol) of ferrocene and 40 g (0,4 mol) of succinic anhydride were dissolved in DCM (700 ml). The solution was cooled to 0-5 ⁰ C using an ice-bath.. 70 g (0,53 mol) of aluminum trichloride was added to the solution in small portions. After completed addition, the solution was allowed to warmed up to room temperature and stirred for additional two hours. The reaction was monitored by TLC (EtOAc/PE , 1 :5). The mixture was poured into ice-water and stirred for 30 min. The organic phase was separated and the aqueous phase was extracted twice with DCM (200 ml). The combined organic phases were dried over Na ₂ SO ₄ and concentrated in vacuo to yield 8Og of crude X-I which was used in the next step without further purification.

b)

X-1 XI-1

To a 1000 ml three-necked flask, equipped with a reflux condenser and a scrubber for HCl gas adsorption, was added 70 g of crude crude X-I and ethanol (700 ml). SOCl ₂ (40 ml) was slowly added to the solution and the solution was stirred at room temperature for 30 min. The reaction mixture was poured into an ice cooled Na ₂ COs solution and stirred for 15 min. The aqueous phase was extracted three times with EtOAc (3x200 ml) and the com- bined organic phases were dried over Na ₂ SO ₄ . After filtration, the solution was concentrated to a volume of approximately 100 ml. The crude product solution was kept at room temperature overnight, and upon filtration, XI-I was isolated as orange crystals. The filtrate was concentrated to dryness and a second crop of XI-I was obtained by column purification (Eluent: EtOAc/PE , 1 :5). ¹ H NMR (CDCl ₃ , 500 MHz): δ 1.29 (t, 2H); 2.69 (t, 2H); 3.07 (t, 2H); 4.20 (q, 2H); 4.26 (s, 5H); 4.33 (s, 2H), 4.80 (s, 2H).

c)

XM XIM

The reaction was conducted under an atmosphere of N ₂ . (S)-CBS (15 g, 0,054 mol) was dissolved in dry THF (50 ml) and cooled to 0-5 ⁰ C using an ice-bath. BH ₃ in THF (50 ml, I M) was added to the solution and stirred for 15 min. XI-I (128 g, 0,41 mol) was dissolved in dry THF (400 ml) and added into the (S)-CBS solution by cannula. The solution temperature was kept below 5 ⁰ C through out the operation. Anther portion of BH ₃ dissolved in THF (200 mL, IM) was added drop wise into the solution via cannula over the course of two hours. Stirring was continued for additional half an hour. The reaction was monitored by TLC (EtOAc/PE , 1 :5). The excess BH ₃ was quenched by drop wise addition Of NH ₄ Cl (sat. aq. solution) to the reaction mixture. The phases were separated and the aqueous phase was extracted three times with EtOAc. The combined organic phases were dried over Na ₂ SO ₄ , and the solvent was removed in vacuo to yield XII-I (1 18 g) as a red-orange oil. The optical purity of XII-I was determined by chiral stationary phase HPLC. Column: AS- H (4,6 x 250 mm, 5μm), mobile phase n-Hexane/IPA 20: 1, Flow rate 0,8 ml/min, Rt _minor = 17,4 min. Rt _major = 18,8.

d)

XV-1 To a solution of XII-I (100 g) was added dry Et ₃ N (100 ml) and DMAP (10 g). The reaction was cooled to 10 ⁰ C using an ice-water bath followed by the addition Of Ac ₂ O (40 g). After 15 minutes of aging, the reaction was left stirring over night at room temperature under an atmosphere of N ₂ . Full conversion was checked by TLC (EtOAc/PE = 1 :5). The solvent was then removed in vacuo and the residue was dissolved in acetonitril (400 ml). 150 mL dimethylamine (150 ml, 33% aq. solution) was added and the mixture was stirred at 45- 50 ⁰ C for 24 hrs until XIII-I disappears on TLC (EtOAc/PE = 1 :5). The solution was poured into water (500 ml) and extracted with EtOAc ( 3x200 ml). The organic phases were combined and dried over Na ₂ Sθ ₄ . The solvent was removed in vacuo to give a dark red oil. The oil was dried under vacuum overnight and subjected to next step without any further purification. The crude XIV-I was dissolved in dry THF (400 ml) slowly added drop wise by cannula into a pre-cooled slurry of LiAlH ₄ (10 g) and THF (100 ml) at 0 ⁰ C. The solu- tion was stirred for additional 2 hours and full conversion checked by TLC (EtOAc as elu- ent). The solution was cooled to -10°C at which temperature water (10 g) was added slowly drop by drop to quench excess LiAlH ₄ . The orange slurry was filter and the filtrate was concentrated in vacuo. After drying under vacuum overnight, the red oil had solidified. The solid (XV-I) was washed with hexane and isolated by filtration (42 g). The filtrate was con- centrated to dryness and additional product was isolated upon silica column chromatography (EtOAc/PE, 1 : 1 ) to yield a red oil (28g).

g)

XV-1 XVM

To a solution of XV-I (26 g) in dry CH ₂ Cl ₂ (100 ml) at O ⁰ C was added TIPSCl (25 g) followed by Et ₃ N (15 mL). The reaction was left to warm to rt and stirred over night under an atmosphere of nitrogen. Full conversion was checked by TLC (EtOAc/PE = 1 :5). The reaction was quenched by the addition of water (50 mL). The organic phase was separated and washed with water (3x100 mL). The organic phase was dried over Na ₂ SO4 and concentrated in vacuo affording a crude product, which was purified by silica column chromatography (ratio EtOAc/PE = 1 :4) to yield XVI-I (34 g) as a red oil. ¹ H NMR (CDCl ₃ , 250 MHz) δ 1.10 (m, 21H), 1.72 (m, 2H), 1.87 (m, IH), 1.98 (s, 6H), 2.19 (m, IH), 3.37 (dd, IH), 3.81 (m, 2H), 4.02 (d, IH), 4.07 (d, IH), 4.11 (s, 7H). ¹³ C NMR (CDCl ₃ , 62.5 MHz) δ 12.0 (3C), 18.1 (6C), 27.8, 30.8, 40.4 (2C), 62.8, 63.5, 66.8, 67.1, 67.3, 68.5 (5C), 69.3, 85.5. LC-MS: Highest Mass detected 457. Most abundant mass 412.

h) XVM xviH

A solution of XVI-I (10 g) in dry diethylether (50 mL) was cooled to -78 ⁰ C. A solution of t-BuLi (16 mL, 1.6 M ) was added and the reaction was left to warm to room temperature. After 3 hours of aging, the mixture was re-cooled to -78 ⁰ C at which temperature Ph ₂ PCl (6 g) was added. The reaction mixture was alowed to warm to room temperature and stirred for additional 6 hours before slowly poured into an ice-cooled saturated aqueous solution of Na ₂ CO ₃ . The mixture was extracted with EtOAc (80 mL) and the combined organic phases were dried over Na ₂ SO ₄ . The organic solvent was removed in vacuo and the residue was flushed through a silica plug (EtOAc/PE = 1 :3) to yield XVl 1-1 a red-orange oil.

i)

Bis-(3,5-Diisopropyl-phenyl) phosphine oxide (0.7 g) was dissolved in dry THF (5 mL ) in a dried Schlenk flask (50 mL volume). The solution was cooled to 0 °C, and then LiAlH ₄ (0.1 g) was added. The mixture was allowed to stir for 2 hours at 0 ⁰ C under an atmosphere of nitrogen. The solvent was removed in vacuo, and the residue was cooled to -78 ⁰ C. A solution of XVII-I (1,0 g) in acetic acid (10 mL) was added into the flask. The mixture was heated at 70 ⁰ C for 1 hour and 80 ⁰ C for 1 hour under N ₂ atmosphere. After cooled to room temperature, 30 ml EtOAc and 10 mL distilled water was added and stirred for several minutes. The solution was filtered and, washed with saturated aqueous Na ₂ CO ₃ . The organic phase was separated and dried over MgSO ₄ . The solvent was removed and the residue was flushed through a silica column (EtOAc/PE = 1:20) to yield XVIII-I as a red oil of 10 (0.8 g).

The red oil of XVIII-I was dissolved in 10 mL of THF. Ig of TBAF was added. The solution was stirred for 24 hrs at 50 ° C under the protection OfN ₂ . 20 mL water was added. The solution was extract with EtOAc (3 x 2OmL). The solvent was removed and the residue was flushed through silica column (EtOAc/PE = 1 :5) to yield 0.6 g of VIII-1,5,1.

General procedure for the synthesis of VIII, Ferrocen carbaldehyde ap- p roach (Route B).

a')

Br _v ^^^OH TIPSCI, Imidazole, Br^^-^OTIPS

To a 250 ml round-bottomed flask was charged 3-bromo-l-propanole (25.0 g, 180 mmoles, 1.00 eq), Tri-/-propylsilyl chloride (34.7 g, 180 mmoles, 1.00 eq), imidazole (30.6 g, 450 mmoles, 2.50 eq) and dichloromethane (150 mL). The reaction mixture was stirred for 60 hours at rt when it was poured into water (200 mL). The aqeuous phase was extracted with dichloromethane (3 x 50 mL) and the combined organic phases were dried over magnesium sulfate and concentrated to yield 53.2 g (100.2 %) of a colorless oil.

b')

XIX-1 XX-1

To a flame-dried round-bottomed flask was charged Magnesium (12.15 g, 500 mmoles, 5.00 eq) and dry THF (80 mL) under Argon. The dispersion was heated to reflux and allowed to cool to just under reflux before Dibromoethane (0.1 mL) was added. The mixture was heated until a vigorous reaction started and allowed to react for a few minutes before it was cooled to 0 ⁰ C on an ice-bath. A solution of (3-Bromopropoxy)-tri-/-propylsilane (29.53 g, 100 mmoles, 1.00 eq) in THF (dry, 20 mL) was added to the cooled dispersion of Magnesium over 45 min by a syringe pump. The resulting reaction gave rise to a constant reaction temperature of 9 ⁰ C. After complete addtion the reaction mixture was stirred for another 30 min when full conversion was observed by GC (sample quenched with water). Ferrocenealdehyde (XIX-I) (17.12 g, 80 mmoles, 0.80 eq) in THF (dry, 40 mL) was added over 30 min at 0 ⁰ C by a syringe pump. The reaction mixture was stirred for another 15 min before the reaction mixture (except the excess magnesium) was poured into a 1 : 1 ammoniumchloride (aq, sat) - water mixture (250 mL, 0 ⁰ C). The excess magnesium was washed with MTBE and added to the THF-water solution. The resulting mixture was extracted with MTBE (3 x 100 mL) and the combined organic phases were dried over magnesium sulfate and concentrated to yield 38.9 g (90% (if purity considered to be 80%)) of a dark brown oil (XX-I).

c')

XX-1 XXM

To a round-bottomed flask was charged the produced alcohol from the previous Grignard reaction in step b') (38.9 g, 80% pure, 72 mmoles), acetic anhydride (30 g, 294 mmoles, 4.0 eq) and pyridine (30 g, 379 mmoles, 5.3 eq). The resulting solution was stirred overnight at rt under Ar when it was poured into water (300 mL) and extracted with MTBE (3 x 75 mL). The combined organic fractions were concentrated to yield 50 g of a dark oil including residues of acetic acid and pyridine. This material was used without purification in the next step. To a round-bottomed flask was charged the crude acetylated product (50 g), aqueous di- methylamine (40 mL, 50% solution, -400 mmoles) and isopropanol (60 mL). The resulting solution was stirred overnight at rt and further Ih at 50 ⁰ C and 2h at 60 ⁰ C before full conversion was observed by TLC. The reaction mixture was poured into water (300 mL) and pH of the aqueous phase measured to be 10. The aqueous solution was extracted with di- ethylether (3 x 75 mL) and the combined organic phases were dried over magnesiumsulfate and concentrated to yield 37 g of a dark viscous oil (XXI-I).

d')

XXI-1 XV1-1

To a solution of amine XXI-I (1.0 g, 2.2 mmol, 1.0 eq) in isopropyl alcohol (10 mL) was added (2R,3R)-2,3-bis(4-methylbenzoyloxy)succinic acid, hereinafter referred to as (-)- DTTA (844 mg, 2.2 mmol, 1.0 eq). The mixture was heated under stirring to homogeneity and was then allowed to cool to room temperature. The mixture was seeded with seeding crystals (10 mg) and left stoppered at -18 ⁰ C overnight. The mixture was decanted and the solid was washed with n-hexane (3 x 4 mL) and dried to give XVI-l(-)-DTTA (839 mg, 46 %) with an enantiomeric excess of 45 %. The salt was recrystallised three times in isopropyl alcohol (salt concentration = 10 % w/v) to provide XVI-l(-)-DTTA (271 mg, 15 %) with an enantiomeric excess of 98 %.

The optical purity of XVI-l(-)-DTTA was established in the following manner: To a small sample (ca. 20 mg) was added tetrahydrofuran (0.5 mL) and 4 M hydrochloric acid (0.5 mL). The mixture was stirred for 30 min and then basified with concentrated sodium hydroxide (1 mL). The mixture was extracted (n-hexane, 2 x 1 mL) and the combined organic phase was dried (sodium sulfate), filtered and evaporated to dryness. The resultant oil was dissolved in n-hexane and analysed by chiral stationary phase HPLC (Column: OD-H Chiralcel. Eluent: 0.1 % diethylamine, 1 % isopropyl alcohol in n-hexane)

The amine XVI-I was liberated in the following way: To a slurry of XVI-l(-)-DTTA (1.00 g, 1.19 mmol) in 4 M sodium hydroxide (50 mL) was added n-hexane (50 mL). The mixture was stirred for 30 minutes before the phases were separated. The aqueous phase was extracted with hexane (3 x 30 mL) and the combined organic phase was washed with 4 M sodium hydroxide (20 mL) and water (50 mL) before drying (sodium sulfate), filtration and concentration in vacuo to give amine XVI-I (476 mg, 84 %) as an orange oil.

The compound XVI-I is converted to a compound falling within general formula (VIII) as provided for under Route A.

Example 3

Ligands prepared using the synthesis protocols outlined in Route A and B.

Table 2

PNMRi(CDCl ₃ , 161 MHz)

¹ H and ³¹ P NMR data for ligands VIII-1,2,1 and VII-1,1,1

VIII- 1 ,2, 1 : ¹ H NMR (CDCl ₃ , 500 MHz) δ: 1 ,27 (s, 9H); 1.30 (s, 9H); 1.44 (m, 1 H); 1.60 (m, IH); 1.91 (m, IH); 2.34 (m, IH); 3.31 (m, IH); 3.44-3.51 (m,2H); 3.89 (s, 5H); 3.98 (s, IH); 4.27 (m, IH), 4.41 (s, IH); 7.14-7.39 (m, 16H); 7.62 (m, 2H). VIM ,1,1

¹ H NMR (CDCl ₃ , 500 MHz). Isomer 1 : δ 1.6 (m, IH), 1.8-2.2 (m, 6H), 2.54 (m, IH), 3.69 (m, IH), 3.78 (s, IH), 4.03 (s, 5H), 4.34 (m, 2H), 7.14-7.17 (m, 10H), 7.39 (m, 3H), 7.59 (m, 2H). Isomer 2: δ 1.6 (m, IH), 1.89 (m, 2H), 2.05 (m, IH), 2.23-2.33 (m, 4H), 3.54 (m, 2H), 3.90 (m, 5H), 3.93 (s, IH), 4.05 (s, IH), 7.03 (m, 2H), 7.20 (m, 2H), 7.31 (m, 2H), 7.41 (m, 5H), 7.68 (m, 2H).

The two isomers was separated by preparative chiral stationary phase HPLC: CHIRALCEL OD-H column: 0.46 cm LD. x 25cm L; mobile phase: Hexane/Isopropanol =98 /2; Flow rate: 1.0 ml/min; Wave length: 254 nm; Temp.: 30 ⁰ C. Isomer 1 : (Rentention time, 5.297 min). Isomer 2: (Rentention time, 6.138 min).

Example 4

Using the procedure outlined in example 1, several experiments were conducted as seen in table 3.

Table 3

Results for the screening of aromatic halides and alkyl halides as additives for the catalytic enantioselective hydrogenation of MEA-imine (Ib) to S-NAA (lib). No acid added to the reaction mixture.

General experimental procedure: The experiments were carried out at 50 ⁰ C, at 30 bar hydrogen pressure, a substrate/catalyst ratio of 40000 and 4 hours reaction time.

'^The experiment was carried out at 5O ⁰ C, at 80 bar hydrogen pressure, a substrate/catalyst ratio of 100000 and 12 hours reaction time.

PFBnBr = 2,3,4,5,6-Pentafiuorobenzylbromide.

Nd = Not determined.

Example 5 To a flame-dried Schlenk flask was added [Ir(cod)Cl] ₂ (3.2 mg, 0.0048 mmoles), ligand VIII-1,8,1 (9.2 mg, 0.0012 mmoles) and dry degassed THF (10.0 mL) under argon to give a yellow colored homogenous solution. To the reaction vessel was added MEA-imine (4.0 g, 19.5 mmoles, 1 eq) and 1,2,3,4,5-pentafluorobenzyl bromide (9.0 μL, 0.059 mmoles, 0.06 mol %). The reaction vessel was sealed and purged three times with nitrogen under stirring before adding 500 μL of the above mentioned catalyst solution through the injector system. The injector system was washed once with dry degassed THF (0.5 mL) before purging three times with hydrogen under stirring. The reaction was initiated by heating to 5O ⁰ C and then introducing high pressure hydrogen (30 bar) to the reaction vessel. After 4 hours the reaction vessel was allowed to reach room temperature before releasing the hydrogen. GC yield >76%, optical purity = 79 % ee.

Example 6

To a flame-dried Schlenk flask was added [Ir(cod)Cl] ₂ (3.9 mg, 0.0058 mmoles, 0.0005 mol%), ligand VIII-1,8,1 (11.2 mg, 0.015 mmoles, 0.0012 mol %) and dry degassed THF (5.0 mL) under argon to give a yellow colored homogenous solution. To the reaction vessel was added MEA-imine (239.7 g, 1 167.6 mmoles, 1 eq) and 1 ,2,3,4,5-pentafluorobenzyl bromide (106 μL, 0.70 mmoles, 0.06 mol %). The reaction vessel was sealed and purged three times with nitrogen under stirring before adding the catalyst solution through the injector system. The injector system was washed once with dry degassed THF (0.5 mL) before purging three times with hydrogen under stirring. The reaction was initiated by heating to 5O ⁰ C and then introducing high pressure hydrogen (80 bar) to the reaction vessel. After 7 hours the reaction vessel was allowed to reach room temperature before releasing the hydrogen. GC yield >99%, optical purity = 79 % ee.

Example 7

To a flame-dried flask was added [Ir(cod)Cl] ₂ (0.76 g, 1,1 mmoles, 0.0005 mol %), ligand VIII-1,8,1 (2.12 g, 2.76 mmoles, 0.0012 mol%) and dry degassed THF (817 g) under argon to give a yellow colored homogenous solution. To the autoclave was added MEA-imine (46 Kg, 224.4 moles, 1 eq) and 1,2,3,4,5-pentafluorobenzyl bromide (35.1 g, 0.13 moles, 0.06 mol %). The reaction vessel was purged three times with nitrogen under stirring followed by three times flushing with hydrogen, before adding the catalyst solution through the injector system. The reaction was initiated by introducing high pressure hydrogen (80 bar) to the reaction vessel and heating to 5O ⁰ C. After 9 hours the reaction vessel was allowed to reach room temperature before releasing the excess hydrogen. GC yield >99%, optical purity = 78 % ee. Example 8

ClCOCH ₂ Cl

(lib) S-NAA (HIb) (5)-Metolachlor

To a 250 mL jacketed reactor equipped with a mechanical stirrer was added S-NAA (lib) (43.3 g, 0.209 mol) prepared according to the procedure in example 1, hexane (55.1 g) and K ₂ CO ₃ (15 g, 10% aq.) at 25°C. A solution of Chloracetyl chloride (24.8 g, 0.219 mol) in hexane (10.6 g) and NaOH (43.9 g, 20% aq.) were parallel and simultaneously added to the reactor during the course of 30 min, keeping the internal reaction temperature below 30°C. The reaction mixture was stirred for additional 10 min. and the two phases were separated. The organic phase was separated and washed with HCl (50 g, 3.1% aq.), then water (40 g) and subsequently concentration in vacuo to give 56.5 g of product, (S)- Metolachlor.