The invention relates to chiral ferrocenes substituted in the 1 - and 1 '-positions by two different radicals and also substituted in the 2-position, according to the general formula (I), to processes for their preparation and to the use thereof as ligands in catalysis.

Metal complexes having chiral ferrocenyl ligands are known as catalysts for a number of reactions (e.g. enantioselective hydrogenation, hyd rosily lation, formation of C-C bonds). The task of the chiral ligands is firstly so to adjust the electronic environment on the metal that a catalytic cycle becomes possible and secondly to transfer the chiral information to the substrate. Hitherto there has been no model that makes it possible to predict which chiral ligand will be best (especially in respect of enantioselectivity) for the catalytic reaction of a substrate. It is therefore advantageous if the electronic and steric properties of a ligand can be coordinated within a wide range both roughly and precisely.

Most of the diphosphine ligands described hitherto, however, contain two identical phosphines. That applies also to the chiral ferrocenyl ligands described by T. Hayashi et al. which have already been used successfully in a large number of catalytic reactions. Those ligands correspond, for example, to the following formula:

and are described in T.Hayashi, Ferrocenes (Ed.: A. Togni and

-§__. PR,

T. Hayashi), VCH Publishers New York (1995) 105-142.

Examples of chiral ferrocenyl ligands having at least one sulfur radical are:

(A) OK. Lai, A.A. Naiini and OH. Brubaker, Inorg. Chim. Acta, 164 (1989)

0^ SR

205-10.

(B) Fe ^s"Me CH. Wang and CH. Brubaker, J. Mol. Catal., 75 (1992) 221-33.

(C) Y. Nishibayashi, K. Segawa, J.D. Singh, S. Fukuzawa, K. Ohe and S.

Uemura, Organometallics, 15 (1996) 370-9.

A synthesis method is described hereinbelow that for the first time makes it possible to prepare chiral ferrocenyl ligands selectively having two different radicals in the 1 ,1 '-position. Preferably the two different radicals are two different phosphine radicals or sulfur radicals or a sulfur radical and a phosphine radical. This makes it possible to adjust the electronic and steric properties of the chiral ferrocenyls according to the invention and of their metal complexes within a very wide range.

The invention relates to compounds of the formula

(I), wherein

Ri is Cι-C ₈ alkyl, C ₅ -C. ₂ cycloalkyl, phenyl or phenyl substituted by from 1 to 3 substituents selected from C C ₄ alkyl and d-C ₄ alkoxy;

Ra is -P(R ₁₀ R. _. ) or -SRι ₂ ;

R _b is -P(R'ιoR'n), -SR' ₁₂ , -CH=NR ₁₂ , -CH ₂ -NH-R ₁₂ or -CH ₂ -O-P(R ₁₀ R.ι);

R ₁₀ and Rn are each independently of the other CrC ₁₂ alkyl, d-C ₁₂ alkyl substituted by

C-Calkoxy, C ₅ -Cι ₂ cycloalkyl or by phenyl, C ₅ -C ₁₂ cycloalkyl, phenyl, C ₅ -C ₁₂ cycloalkyl substituted by C C ₄ alkyl or by C ₁ -C ₄ alkoxy, or phenyl substituted by from one to three substituents selected from C C alkyl, C-Calkoxy, -SiR ₄ R ₅ R ₆ , halogen, -SO ₃ M, -CO ₂ M,

-PO ₃ M, -NR ₇ R ₈ , -ΓNR ₇ R ₈ R ₉ ]X ^' and C.-C ₅ fluoroalkyl; or

R ₁₀ and Rn together are C -C ₈ alkylene, C -C ₈ alkylene substituted by C C ₄ alkyl or by phenyl, or annelated C ₄ -C ₈ alkylene;

R' ₁₀ and R'n are each independently of the other as defined for R ₁₀ and Rn , with the proviso that -P(RιoRn) is not identical to -P(R'.oR'n);

R ₁₂ is H, C C ₁₂ alkyl, C Cι ₂ alkyl substituted by C C ₄ alkoxy, C ₅ -Cι ₂ cycloalkyl or by phenyl,

C ₅ -Cι ₂ cycloalkyl, phenyl, C ₅ -C ₁₂ cycloalkyl substituted by C _r C ₄ alkyl or by C C ₄ alkoxy, or phenyl substituted by from one to three substituents selected from CrC ₄ alkyl, d-C ₄ alkoxy,

-SiR ₄ R ₅ R ₆ , halogen, -SO ₃ M, -CO ₂ M, -PO ₃ M, -NR ₇ R ₈ , -fNR ₇ R ₈ R ₉ ]X ^' and C C ₅ fluoroalkyl;

R'ι ₂ is as defined for R ₁₂ , with the proviso that -SRι ₂ is not identical to -SR' ₁₂ ;

R ₄ , R ₅ and R ₆ are each independently of the others C Cι ₂ alkyl or phenyl;

R ₇ and R ₈ are each independently of the other H, d-Cι ₂ alkyl or phenyl, or

R ₇ and R ₈ together are tetramethylene, pentamethylene or 3-oxa-1 ,5-pentylene,

R ₉ is H or C _r C ₄ alkyl;

M is H or an alkali metal;

X ^" is the anion of an acid;

Y is -OR ₁₃ , -SR ₁₄ or -NR ₁₅ R. ₆ ;

Rι ₃ is H, d-Ciβalkyl, -C(O)-d- ₈ alkyl, phenyl or phenyl substituted by from one to three substituents selected from C C ₄ alkyl, d-C ₄ alkoxy, -SiR ₄ R ₅ R ₆ , halogen, -SO ₃ M, -CO ₂ M,

-PO ₃ M, -NR ₇ R ₈ , -[ ⁺ NR ₇ R ₈ R ₉ ]X ^' and C C ₅ fluoroalkyl;

R ₁₄ is H, C,-C ₁₈ alkyl, phenyl or phenyl substituted by from one to three substituents selected from d-dalkyl, C C ₄ -alkoxy, -SiR ₄ R ₅ R ₆ , halogen, -SO ₃ M, -CO ₂ M, -PO ₃ M, -NR ₇ R ₈ ,

-[ ⁺ NR ₇ R ₈ R ₉ ]X ^" and C C ₅ - fluoroalkyl; and

R ₁₅ and Rι ₆ are each independently of the other d-Cι ₈ alkyl that may be substituted and/or interrupted by one or more hetero atoms, arylenes or carbocycles; or

-NR ₁₅ R ₁₆ is a cyclic amine.

Preferred compounds of formula (I) are those in which R _a is -P(R.oRn) and R _b is -P(R'ιoR'n), at least one substituent R ₁₀ , R' _. o, Rn or R'n having a chemical structure that is different from the other substituents; especially preferably R ₁₀ and R' ₁₀ and also Rn and R'n have a different chemical structure from one another.

Examples of Rx as alkyl are methyl, ethyl, n-propyl and isopropyl, n-butyl, isobutyl and tert- butyl, pentyl, hexyl, heptyl and octyl. Linear alkyl is preferred. It contains preferably from 1 to 4 carbon atoms. Methyl and ethyl are preferred, with methyl being especially preferred.

Ri as cycloalkyl preferably contains from 5 to 8, especially 5 or 6, ring carbon atoms. Examples of cycloalkyl are cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl and cyclododecyl. Cyclopentyl and cyclohexyl are preferred, with cyclohexyl being especially preferred.

R _T contains as substituted phenyl preferably 1 or 2 substituents. Alkyl substituents may be, for example, methyl, ethyl, n-propyl and isopropyl, n-butyl, isobutyl and tert-butyl, with methyl and ethyl being preferred. Alkoxy substituents may be, for example, methoxy, ethoxy, n-propoxy and isopropoxy, n-butoxy, isobutoxy and tert-butoxy, with methoxy and ethoxy being preferred. In a group of compounds of formula I, Rt is preferably phenyl or phenyl substituted by 1 or 2 d-C ₄ alkyl or Cι-C ₄ alkoxy substituents.

Rio, Ri ι and Rι ₂ , and R'ι ₀ , R'n and R' ₂ , as alkyl may be linear or branched and contain preferably from 1 to 8, especially from 1 to 4, carbon atoms. Examples of that alkyl are methyl, ethyl, n-propyl and isopropyl, n-butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl. Methyl, ethyl, n-propyl and isopropyl, n-butyl, isobutyl and tert-butyl are preferred. When R ₁₀ and Rn, and R' ₁₀ and R'n, are identical, as alkyl they are especially isopropyl or tert-butyl.

R ₁₀ , Rn and Rι ₂ , and R' ₁₀₎ R'n and R' ₁₂₎ as substituted alkyl are derived from the above- mentioned alkyl, with alkyl having from 1 to 3 carbon atoms being especially preferred. Phenyl is preferred as substituent. Examples of that alkyl are benzyl, 1- and 2-ethylphenyl and n-propylphenyl and isopropylphenyl.

Rio, Ri ι and R. ₂ , and R'10, R'n and R' ₁₂ , as cycloalkyl preferably contain from 5 to 8, especially 5 or 6, ring carbon atoms. Examples of cycloalkyl are cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl and cyclododecyl. Cyclopentyl and cyclohexyl are preferred, with cyclohexyl being especially preferred.

The cycloalkyl may be substituted, for example by from 1 to 3 alkyl or alkoxy substituents. Examples of such substituents have been given above. Methyl and ethyl and methoxy and ethoxy are preferred. Examples of substituted cycloalkyl are methyl- and methoxy- cyclopentyl and -cyclohexyl.

R ₁₀ , Rn and R ₁₂ , and R' ₁₀ , R'n and R'ι ₂ , as substituted phenyl preferably contain 1 or 2 substituents. When the phenyl contains 2 or 3 substituents, those substituents may be identical or different.

Examples of the substituents alkyl and alkoxy have been given above; preferred alkyl and alkoxy substituents for phenyl are methyl, ethyl and also methoxy and ethoxy.

When the phenyl substituent is halogen, it is preferably -F, -Cl or -Br.

When the phenyl substituent is d-Csfluoroalkyl, it is wholly or partially fluorinated Cι-C ₅ alkyl. Examples thereof are the position isomers of mono- to deca-fluoropentyl, mono- to octa-fluorobutyl, mono- to hexa-fluoropropyl, mono- to tetra-fluoroethyl and mono- and di- fluoromethyl. Of the partially fluorinated alkyl radicals, those of the formulae -CF ₂ H and -CF ₂ (d-C ₄ alkyl) are especially preferred. A perfluorinated alkyl is especially preferred. Examples thereof are perfluoropentyl, perfluorobutyl, perfluoropropyl, perfluoroethyl and especially trifluoromethyl. The fluoro-substituted alkyl groups are preferably bonded in the 3-, 4- and 5-positions.

When R ₀ and Rn together are C ₄ -C ₈ alkylene, C ₄ -C ₈ alkyiene substituted by d-C ₄ alkyl or by phenyl, or annelated C -C ₈ alkylene, they are preferably a radical of formula IV, IVa, IVb or IVc

R ₄ , R ₅ and R ₆ may be linear or branched alkyl that preferably contains from 1 to 8, especially from 1 to 4, carbon atoms. Examples of alkyl have been given above. Preferred alkyl is methyl, ethyl, n-propyl, n-butyl and tert-butyl. Especially preferably the substituent -SiR ₄ R ₅ R ₆ is trimethylsilyl.

Of the acidic phenyl substituents -SO ₃ M, -CO ₂ M and -PO ₃ M, the groups -SO ₃ M and -CO ₂ M are preferred. M is preferably H, Li, Na or K.

R ₇ and R ₈ contain as alkyl preferably from 1 to 6, especially from 1 to 4, carbon atoms. The alkyl is preferably linear. Preferred examples are methyl, ethyl, n-propyl and n-butyl. R ₉ as alkyl is preferably methyl.

X ^' as an anion of an acid is preferably Cl ^" , Br ^" or the anion of a carboxylic acid, for example formate, acetate, trichloroacetate or trifluoroacetate, or BF ₄ ^" , PF ₆ ^" or SO ₄ ^2" .

Preferred examples of R ₁₀ , Rn and R ₁₂ , and R' ₁₀₎ R'n and R'ι ₂ , as substituted phenyl are 2- methyl-, 3-methyl-, 4-methyl-, 2- or 4-ethyl-, 2- or 4-isopropyl-, 2- or 4-tert-butyl-, 2-methoxy-, 3-methoxy-, 4-methoxy-, 2- or 4-ethoxy-, 4'trimethylsilyl-, 2- or 4-fluoro-, 2,4-difluoro-, 2- or 4-chloro-, 2,4-dichloro-, 2,4-dimethyl-, 3,5-dimethy!-, 2-methoxy-4-methyl-, 3,5-dimethyl-4- methoxy-, 3,5-dimethyl-4-(dimethylamino)-, 2- or 4-amino-, 2- or 4-methylamino-, 2- or 4- (dimethylamino)-, 2- or 4-SO ₃ H-, 2- or 4-SO ₃ Na-, 2- or 4-[ ⁺ NH ₃ CI ^" ]-, 3,4,5-trimethyl-, 2,4,6- trimethyl-, 4-trifluoromethyl- and 3,5-di-(trifluoromethyl)-phen-1-yl.

Especially preferably Rι ₀ , Rn and Rι ₂ , and R' ₁₀ , R'n and R' ₁₂ , are cyclohexyl, n-butyl, sec- butyl, tert-butyl, phenyl, 2- or 4-methylphen-1-yl, 2- or 4-methoxyphen-1-yl, 2- or 4- (dimethylamino)phen-l-yl, 3,5-dimethyl-4-(dimethylamino)phen-1-yl and 3,5-dimethyl-4- methoxyphen-1-yl, with cyclohexyl, phenyl, 4-methylphen-1-yl and n- and tert-butyl being especially preferred.

R ₁₃ and R ₄ may be as defined hereinbefore by way of example for alkyl and substituted phenyl. Preferably R ₁₃ and R ₁₄ are H, d-C alkyl or phenyl.

R ₁₅ and R ₁₆ may be linear or branched C Cι ₈ alkyl analogously to the definitions given hereinbefore by way of example.

R15 and R ₁₆ as substituted alkyl may be C Cι ₈ alkyl substituted by halogen, -OH, d-C ₈ alkoxy, aryloxy (such as phenyloxy or substituted phenyloxy), -SH, d-C ₈ alkylthio, arylthio (such as thiophenyl), -NH ₂ , primary or secondary Cι-C ₈ amine or by aryl (such as phenyl or naphthyl).

R ₁₅ and R ₁₆ as alkyl interrupted by one or more hetero atoms, arylenes or carbocycles may be alkyl comprising groups such as -(CH ₂ CH ₂ O)-, -(CH ₂ CH ₂ CH ₂ O)-,

-(CH ₂ CH ₂ S)-, -(CH ₂ CH ₂ CH ₂ S)-, -(CH ₂ CH ₂ NH)-, -(CH ₂ NHCH ₂ )-, -(CH ₂ N(Cι-C ₈ alkyl)CH ₂ )-,

-(CH ₂ (C ₆ H ₄ ))- or -(CH ₂ (C ₆ H ₁₀ ))-.

R ₁₅ and R ₁₆ as cyclic amine may be unsubstituted or substituted cyclic amines having a ring size of from 4 to 10, especially 5 or 6, atoms. Substituents are, for example, Cι-C ₈ alkyl or CrC ₈ alkylamine. In addition to the amine function, the ring may contain further hetero atoms, for example -O-, -S-, -NH- or -Nalkyl- .

Preferably Y is the group -NR ₁₅ R ₁₆ . Especially preferably -NR15R.6 is -N(CH ₃ ) ₂ , -N(C ₂ H ₅ ) ₂ , -N(n-C ₃ H ₇ ) ₂₎ -N(iso-C ₃ H ₇ ) ₂ , -N(n-C ₄ H ₉ ) ₂ , pyrrolidyl, piperidyl, -N(CH ₃ )CH ₂ C ₃ F ₇ , -N(CH ₃ )C ₂ H ₄ OH, -N(CH ₃ )C ₂ H ₄ OCH ₃ , -N(CH ₃ )CH(CH ₂ OH) ₂ , -N(CH ₃ )CH(CH ₂ OH) ₂ , -N(CH ₃ )C ₂ H ₄ N(CH ₃ ) ₂ , -N(CH ₃ )C ₂ H ₄ N(CH ₃ )H, -N(CH ₃ )C ₂ H ₄ N(C ₂ H ₅ ) ₂ , -N(C ₂ H ₄ OH) ₂ , -N(CH ₃ )C ₂ H ₄ N(C ₅ H ₁₀ ), -N(CH ₃ )C ₂ H ₄ N(C ₂ H ₄ OC ₂ H ₄ ) or -N(CH ₃ )C ₂ H ₄ N(C ₂ H ₄ OC ₂ H ₄ OC ₂ H ₄ N(CH ₃ )C ₂ H ₄ OC ₂ H ₄ OC ₂ H ₄ ).

Compounds of the formulae

■ ^wnere i ⁿ the substituents have the above-mentioned definitions

and preferred meanings, are especially preferred.

The compounds of formula (I) according to the invention can be obtained in accordance with the following process.

Starting from a compound of formula (II)

(II), wherein

Ri is d-C ₈ alkyl, C ₅ -Cι ₂ cycloalkyl, phenyl or phenyl substituted by from 1 to 3 substituents selected from d-C alkyl and Cι-C ₄ alkoxy;

R ₂ and R ₃ are each independently of the other hydrogen or C.-Cι ₂ alkyl; that compound is reacted in an inert organic solvent first with one equivalent of alkyl-lithium and then, in the presence of an amine complexing agent for Li, with a second equivalent of alkyl-lithium, and the product is then reacted with a halogenating agent to form compounds of formula (III)

wherein Hal is F, Cl, Br or I.

R ₂ and R ₃ as alkyl may be linear or branched. Examples of d- to C ₈ -alkyl have been given above; additionally there may be mentioned the various isomers of nonyl, decyl, undecyl and dodecyl. R ₂ and R ₃ may also be bonded to one another and may form a cyclic alkyl group. Examples are pyrrolidine or piperidine.

Preferably R ₂ and R ₃ are each independently of the other methyl or ethyl; especially preferably they are both methyl.

An example of an amine complexing agent for Li is N,N,N,N-tetramethylethylenediamine.

Within the context of this invention, alkyl-lithium is to be understood as being preferably tert- butyl-, sec-butyl- or n-butyl-lithium.

Halogenating agents are known in the general prior art for many reactions. For example, a number are mentioned in Gmelin, Handbuch der Anorganischen Chemie (Handbook of Inorganic Chemistry), Ferroorganic Compounds Part A Ferrocene 7, Eighth Edition, Springer Verlag 1980, pages 128-136.

Preferably the halogenating agent is selected from the group consisting of Cl ₂ , hexachloroethane, 1 ,2-dichlorotetrafluoroethane, toluene-4-sulfonyl chloride, Br ₂ , 1 ,2- dibromotetrachloroethane, 1 ,2-dibromotetrafluoroethane, toluene-4-sulfonyl bromide, 2,3-

dimethyl-2,3-dibromobutane, l ₂ , 1 ,2-diiodotetrafluoroethane, perfluoropropyl iodide, perfluoroethyl iodide, toluene-4-sulfonyl iodide and perfluoromethyl iodide.

In a first step alkyl-lithium is added to the compounds of formula (III) in an inert organic solvent and allowed to react and then in a second step an organic solution of a compound of formula CIP(Rι ₀ Rn) (Va) or of formula R ₁₂ SSRι ₂ (Vb) is added, yielding compounds of formula

Fe p(R R (Vlb), wherein R ₁₀ , Rn and R ₁₂

have the definitions and preferred meanings given above.

The substitution by the halogen atom takes place predominantly on the cyclopentadienyl ring that carries the second substituent (alkyiamine).

The process is preferably carried out by adding alkyl-lithium at a temperature of from -90 to +30°O

In the second step, the compounds of formula (Va) or (Vb) are preferably added at a temperature of from -90 to +30°C

The compounds of formula (Vlb) are novel and constitute a further aspect of this invention.

The compounds of formula (la) are obtainable by adding alkyl-lithium to compounds of formula (Via), in an inert organic solvent, analogously to the above preparation process for the preparation of compounds of formula (Via), causing the mixture to react and subsequently in a second step adding an organic solution of a compound of formula CIP(R' ₁₀ R ^, ιι) (Vd), wherein R' ₁₀ and R'n have the definitions and preferred meanings given above, and optionally converting the radical -NR ₂ R ₃ into the radical -Y.

The compounds of formula (lb) are obtainable by adding alkyl-lithium to compounds of formula (Via), in an inert organic solvent, analogously to the above preparation process for the preparation of compounds of formula (Vlb), causing the mixture to react and

subsequently reacting it with an organic solution of a compound of formula R' ₁₂ SSR'ι ₂ (Vc), wherein R'ι ₂ has the definitions and preferred meanings given above, and optionally converting the radical -NR ₂ R ₃ into the radical -Y.

Compounds having SR ₁₂ or SR' ₁₂ wherein Rι ₂ or R' ₁₂ is hydrogen can be prepared analogously to "Ferrocenes, Editors A. Togni and T. Hayashi, VCH Publishers 1995", pages 231-233.

The compounds of formulae (lc) and (Id) are obtainable by adding alkyl-lithium to compounds of formula (Vlb), in an inert organic solvent, analogously to the above preparation process for the preparation of compounds of formula (Via) or (Vlb), causing the mixture to react and subsequently reacting it with an organic solution of a compound of formula CIP(R' ₁₀ R'n) (Vd) or of formula R' ₁₂ SSR'ι ₂ (Vc), wherein R ₁₀ , Rn and R' ₁₂ have the definitions and preferred meanings given above, and optionally converting the radical -NR ₂ R ₃ into the radical -Y.

The preparation of the compounds of formulae (I) and especially (la), (lb), (lc) and (Id) constitutes a further aspect of this invention.

The compounds of formula (I), (Via) or (Vlb) may be obtained in the form of racemates, pure enantiomers or mixtures of enantiomers. If the synthesis is carried out using enantiomerically pure compounds of formula (II) as starting materials, there are formed very preferentially only one of the two possible diastereoisomers of the compounds of formula (III) and consequently also of the compounds of formulae (Via) and (Vlb) and (I).

If racemates or optically active mixtures are used as starting materials, they can be separated into the stereoisomers by means of known methods, with chromatographic methods or crystallisation generally being preferred.

Isolation and purification of the compounds is carried out in accordance with methods known perse, for example distillation, extraction, crystallisation and/or chromatographic methods.

The compounds of formula (I) wherein R _b is -CH=NR _i2 or -CH ₂ -NH-R ₁₂ can be prepared starting from a compound of formula (Via) or (Vlb) by converting the halogen radical into a radical -CHO and subsequently reacting the product with a primary amine. The radical -CH=NRi ₂ can be converted into the radical -CH ₂ -NH-Rι ₂ by further reaction with a reducing agent, such as LiAIH ₄ . The general reaction conditions are known to the person skilled in the art and may be generalized from the following Examples.

The compounds of formula (I) wherein R _b is -CH ₂ -O-P(Rι ₀ Rn) can be prepared starting from a compound of formula (Via) or (Vlb) by converting the halogen radical into a radical -CHO and subsequent reduction with a reducing agent, such as LiAIH ₄ , to form the alcohol, which is reacted with a chlorophosphine of formula CIP(RιoRn). The general reaction conditions are known to the person skilled in the art and may be generalized from the following Examples.

To prepare further compounds of formulae (I) and especially (la), (lb), (lc) and (Id), the group NR ₂ R ₃ can be converted into the various groups defined for Y in accordance with the following scheme.

acetic acid

Other alternative or subsequent process steps are known to the person skilled in the art.

A further aspect of this invention is constituted by transition metal complexes with ferrocenyl ligands of formula (I) and especially (la), (lb), (lc) or (Id). d ⁸ -Transition metals, such as Rh, Ir, Ru, Pd, Ni and Au, are preferred, with Rh, Pd, Ni and Ir being especially preferred.

The transition metal complexes according to the invention can be used as catalysts, for example in hydrogenations, transfer hydrogenations and hydrosilylations of double bonds (C-C, C-O or C-N), allylic substitutions, hydroformylations or cross-coupling reactions. The individual, preferably enantioselective, catalytic reactions are known from the literature, for example, also with diphosphine ligands, and the catalysts according to the invention make it possible to vary the catalyst properties in a hitherto unknown manner by means of the two different ferrocenyl radicals. The widely differentiated electronic and steric environments that are thus possible on the transition metal make it possible to increase the stereo- selectivity, activity and/or productivity. A further aspect of this invention is accordingly the use of transition metal complexes containing a compound of formula (I), and especially (la), (lb), (lc) or (Id), in enantioselective catalysis.

The processes for the preparation of the transition metal complexes are analogous to those described in the literature and known to the person skilled in the art. The transition metal complexes are frequently prepared in situ, that is to say in the reaction medium in question. For example, in that process a ligand substitution by the ferrocenyls according to the invention is effected on the transition metal.

The definitions and preferred meanings for the individual substituents of the compounds of formula (I) and especially of formulae (la), (lb), (lc) and (Id) apply analogously also to the transition metal catalysts, to their preparation and to their use.

The following Examples illustrate the invention.

General process procedure:

All operations are carried out under an inert gas atmosphere (argon). Ether and THF are freshly distilled over sodium/benzophenone. Hexane and pentane are dried over a Pb/Na alloy. Unless specified to the contrary, Merck 60 silica gel is used as solid phase for the purification by chromatography.

Abbreviations used:

TMEDA: N,N,N,N-tetramethylethylenediamine n-BuLi or BuLi: n-butyllithium (1.6 molar solution in hexane)

COD: 1 ,5-cyclooctadiene

Cyh: cyclohexyl o-Tol: o-tolyl

Tol: toluene NBD: norbornadiene Hex: hexane Ph: phenyl Me: methyl Cyp: cyclopentyl Cp: cyclopentadienyl t-Bu: tert-butyl Ac: acetyl

Example A2 Preparation of the compound of formula 2 (R)-N,N-Dimethyl-1-[(S)-1\ 2 bis(bromo)-ferrocenyl]ethylamine

- Br (2)

20.6 ml (33 mmol) of a 1.6M n-BuLi solution are added dropwise at room temperature, with stirring, to a solution of 7.71 g (30 mmol) of (R)-N,N-dimethyl-1-ferrocenylethylamine in 50 ml of diethyl ether. After 1.5 hours a further solution consisting of 22.5 ml (36 mmol) of a 1.6M BuLi solution in hexane and 4.95 ml (33 mmol) of TMEDA is added dropwise and the reaction mixture is stirred overnight. The dark-brown, cloudy reaction mixture is then cooled to from -72 to -78°C using a dry ice/isopropanol bath and, with stirring, 7.9 ml (66 mmol) of 1 ,2-dibromotetrafluoroethane are slowly added dropwise in such a manner that the temperature of the mixture does not exceed -74°C The mixture is stirred for a further 1 hour with cooling and then for a further 2 hours without cooling. 50 ml of ice-water are added to the resulting orange suspension and extraction is carried out by shaking with 25 ml of ethyl acetate several times. The organic phases are collected, washed with water, dried with Na ₂ SO ₄ and concentrated using a rotary evaporator. The brown crude product is purified by chromatography (silica gel: Merck 60; eluant: acetone). 7.5 g of compound 2 are obtained (yield 60%, brown oil).

Analysis:

1H-NMR (CDCI ₃ ): δ 1.53 (d, 3H, J = 7, C-CH ₃ ), 2.13 (s, 6H, N(CH ₃ ) ₂ ), 3.78 (q, 1 H, J = 7, CH-

Me), 4.03-4.5 (m, 7H, C ₅ H ₃ FeC ₅ H ₄ ).

Microanalysis calculated for Cι ₄ H ₁₇ NBr ₂ Fe: C, 40.52; H, 4.13; N, 3.38; Br, 38.51 ; Fe, 13.46.

Found : C, 40.80; H, 4.10; N, 3.30; Br, 38.18.

Examples A4-A8:

The method is described using the example of compound (4). All the other compounds are prepared analogously. Different conditions and the results are given in Table 1.

Example A4 Preparation of the compound of formula 4

(R)-N,N-Dimethyl-1 -[1 '-(bromo), (S)-2-(diphenylphosphino) ferrocenyljethylamine

12.2 ml of a 1.6M BuLi solution in hexane (1 mmol of BuLi per mmol of starting material) are added dropwise at -30°C, with stirring, to a solution of 7.98 g (19.2 mmol) of compound (2) in 96 ml of diethyl ether (5 ml per mmol of starting material). The mixture is then cooled to from -78 to -70°C and 4.23 ml of CI-PPh ₂ (1.2 mmol of chloro-phosphine per mmol of starting material) are slowly added. The mixture is then allowed to warm to room temperature and is stirred for a further 2 hours. Water is then added to the resulting yellow suspension and extraction is carried out by shaking with hexane several times. The organic phases are collected, washed with water, dried with Na ₂ SO ₄ and concentrated by rotary evaporation. The yellow-brown crude product is purified by chromatography (first, crude purification with silica gel: Merck 60; eluant: ethyl acetate, then chromatography over Alox; eluant toluene/hexane 1 :10). 5.27 g of product are obtained (yield 53 %, orange-brown, almost solid).

The selectivity and yield of the reaction can be increased further if a nonpolar solvent is used. In pentane, instead of diethyl ether, a yield of more than 60% is obtained.

Analysis:

1H-NMR (CDCI ₃ ): δ 1.25 (d, 3H, J = 7, C-CH ₃ ), 1.75 (s, 6H, N(CH ₃ ) ₂ ), 4.15 (m, 1 H, J = 7,

CH-Me), 3.7-4.4 (m, 7H, C ₅ H ₃ FeC ₅ H ₄ ), 7.1-7.65 (m, 10H, P(C ₆ H ₅ ) ₂ )

³ P-NMR (CDCI ₃ ): δ -24.6

The optical purity can be verified by means of 1H-NMR by the formation of a complex of (4) with di-μ-chloro-[(R)-dimethyl(α-methylbenzyl)aminato-C2-N]dipa lladium(ll) (J. Chem. Soc, Dalton Trans., (1979) 2019): no trace of the other enantiomer is observed.

Table t :

Diethyl ether is used as solvent except in the case of compound 4, when hexane is used.

Examples 1-11 :

The method is described using the example of compound (100). All the other compounds are prepared analogously. Different conditions and the results are given in table form (see Table 2):

2) CI-P(R") ₂

'Br < __ P(R") ₂

Example 1 : Preparation of (R)-N,N-dimethyl-1-[1'-(dicyclohexylphosphino), (S)-2- (diphenyiphosphino) ferrocenyl]ethylamine

(4) (100)

2.16 ml of a 1.6M BuLi solution in hexane (1.2 mmol of BuLi per mmol of starting material) are added dropwise at -30°C, with stirring, to a solution of 1.5 g (2.88 mmol) of (4) in 20 ml of diethyl ether (7 ml per mmol of starting material). The mixture is then cooled to from -78 to -70°C and 0.84 g of chloro-dicyclohexylphosphine (1.25 mmol of chloro-phosphine per mmol of starting material) is slowly added. The mixture is then allowed to warm to room temperature and is stirred for a further 2 hours. Water is then added to the resulting yellow suspension and extraction is carried out by shaking with ethyl acetate several times. The organic phases are collected, washed with water, dried with Na ₂ SO and concentrated by rotary evaporation. The yellow-brown crude product is purified by chromatography (silica gel: Merck 60; eluant: ethyl acetate/hexane 1/3). 1.33 g of product are obtained (yield 72.5 %, orange powder). ³¹ P-NMR (CDCI ₃ ): δ -8.1 (PCyh ₂ ), -23.4 (PPh ₂ )

Table 2: Synthesis of the diphosphine compounds:

y ^NMe * D BUU ^ ^Me ₂ ττ ^p (R') ₂ „ τ ^p (R') ₂

Comp. R' R" Start¬ Amount Purification Yield 31 p 31 p No. ing mmol Eluant % δPR' ₂ δPR" ₂ mat. of start¬ Ex. ing No. mat.

100 Ph Cyh A4 2.9 ethyl acetate 73 -23.4 -8.1 1/Hex 3

101 Ph Cyp A4 1.76 ethyl acetate 57 -23.2 -11.3 1/Hex 3

102 Ph o-Tol A4 2.9 ethyl acetate 30 -23.6 -37.6 1/Tol 2

103 Ph Ph-p-CF ₃ A4 0.58 ethyl acetate 30 -24.1 -17.1 1/Hex 1

104 Cyh Ph A5 0.3 ethyl acetate 54 -11.4 -18.0 1/Hex 8

105 Ph-p-CF ₃ Cyh A6 0.29 Hex 47 -22.7 -8.5

106 Ph-p-CF ₃ Ph A6 0.46 ethyl acetate 40 -23.0 -18.0

107 Ph-p-CF ₃ t-Bu A6 0.46 ethyl acetate 62 -22.9 +26.8 1/Hex 2

108 Cyp Ph A7 0.71 ethyl acetate 84 -20.4 -17.6 1/MeC1 1

109 o-Tol Cyh A8 2.1 ethyl acetate, 82 -45.0 -6.2 0.5 % NEt ₃

110 o-Tol Ph A8 2.0 ethyl acetate, 73 -45.4 -16.1 0.5 % NEt ₃

Merck 60 silica gel is used as the solid phase except in the case of compound 105, when Alox is used.

Example 12:

(2) (10)

4.97 ml (7.95 mmol) of BuLi are added dropwise at approximately -40°C over a period of 30 minutes to a solution of 3 g (7.23 mmol) of compound (2) in 42 ml of pentane, and the mixture is stirred at that temperature for a further 30 minutes. The mixture is then cooled to -78°C and 2.05 g (9.4 mmol) of phenyl disulfide are added, cooling is removed and the mixture is stirred overnight. Saturated sodium hydrogen carbonate solution is then added to the reaction mixture and extraction is carried out 3 times with ethyl acetate. The combined organic phases are washed with saturated NaCI solution, dried over sodium sulfate, concentrated by rotary evaporation and purified by chromatography (first, silica gel: Merck 60; eluant: acetone, then Alox III; eluant: hexane / 0.5% triethylamine). 1.41 g of product (100) are obtained (yield 44%, yellow powder).

Example 13:

(10) (111 )

0.93 ml (1.49 mmol) of BuLi is added dropwise at approximately -40°C to a solution of 600 mg (1.35 mmol) of compound (10) in 5 ml of diethyl ether, and the mixture is stirred at that temperature for a further 30 minutes. The mixture is then cooled to -78°C and 0.33 ml (1.76 mmol) of chloro-diphenylphosphine is added, cooling is removed and the mixture is stirred overnight. Water is then added to the reaction mixture and extraction is carried out 3 times with ethyl acetate. The combined organic phases are washed with saturated NaCI solution, dried over sodium sulfate, concentrated by rotary evaporation and purified by chromatography (silica gel: Merck 60; eluant: acetone). 0.72 g of product is obtained (yield 97 %, orange oil).

Example 14:

(10) (113)

Starting with 600 mg of compound (10), compound (113) is prepared in nalogy to compound (111 ). 0.63 g of product is obtained (yield 83 %, orange oil).

Example 15:

(4) (112)

0.83 ml (1.3 mmol) of BuLi is added dropwise at -40°C over a period of 30 minutes to a solution of 626 mg (1.2 mmol) of compound (4) in 10 ml of diethyl ether, and the mixture is stirred at that temperature for a further 30 minutes. The mixture is then cooled to -78°C and 341 mg (1.56 mmol) of phenyl disulfide are added, cooling is removed and the mixture is stirred overnight. Saturated sodium hydrogen carbonate solution is then added to the reaction mixture and extraction is carried out 3 times with ethyl acetate. The combined organic phases are washed with saturated NaCI solution, dried over sodium sulfate, concentrated by rotary evaporation and purified by chromatography (silica gel: Merck 60; eluant: hexane/ethyl acetate 2:1 with 1 % triethylamine). 568 mg of product are obtained (yield 86%, red oil).

Example 16:

(4) (17)

(4) (18)

Compound (17):

(17) is prepared analogously to (11 ) starting from 0.48 mmol of (4) and 0.64 mmol of dibenzyl disulfide (duration of the reaction 12 hours). The crude product is extracted in water/ethyl acetate and purified by chromatography (eluant: ethyl acetate). Yield: 70% (orange, almost solid oil)

Compound (18):

(18) is prepared analogously to (17). Purification by chromatography (eluant: hexane/ethyl acetate 1 : 1) yields the product in a yield of 86% (orange, almost solid oil).

Characteristic NMR signals of compounds containing sulfur:

^r,

Comp R R' ¹ H-NMR (δ) ³¹ P-NMR (δ)

No.

(10) S-Ph Br 7.00 - 7.25 (m, 5H, SPh)

(111) S-Ph PPh ₂ 6.95 - 7.20 (m, 5H, SPh) - 18.3

7.20 -7.45 (m, 10H, PPh ₂ )

(113) S-Ph P(Cyh) ₂ 0.9 - 1.4 (m, PCyh ₂ ) - 8.66

6.95 - 7.20 (m, 5H, SPh)

(112) PPh ₂ S-Ph 1.38 (d, 3H, J=7, CH-CH ₃ ) - 24.4

6.95 - 7.55 (m, 15H, SPh and PPh ₂ )

(17) PPh ₂ S-CH ₂ -Ph 3.66 (s, 2H, CH ₂ -Ph) - 22.6

(18) PPh ₂ S-Cyh 2.5 (m, 1H, S-CH) - 22.4

Example 17:

y ~ _Br 2) N,N-Dimethylformamide /Cλ /C

(4) (11 ) (12)

Compound (11 ):

1.3 Equivalents of a 1.6M solution of n-butyllithium in hexane are added dropwise at approximately -40°C to a solution of 2.88 mmol of (4) in diethyl ether (10 ml per mmol of (4)), and the mixture is stirred at that temperature for a further 30 minutes. The reaction with

2.8 mmol of N,N-dimethylformamide is carried out at -78°C The reaction mixture is then stirred at 25°C for 4 hours, concentrated by rotary evaporation and extracted in toluene/water. The organic phase is dried with sodium sulfate and concentrated by rotary evaporation, and the crude product is purified by chromatography (silica gel Merck 60, eluant: hexane/ethyl acetate 1 :1). Yield 84% (red, viscous oil).

Compound (12):

A mixture of 0.46 mmol of (11) in diethyl ether (10 ml per mmol of starting material) and

1.9 mmol of lithium aluminium hydride is stirred at room temperature for 2 hours. There are then added first 0.2 ml of water and, once the evolution of hydrogen has subsided, diethyl ether and sodium sulfate, the mixture is filtered, the solution is concentrated by rotary evaporation and the crude product is purified by chromatography (eluant: ethanol). Yield 80% (red viscous oil).

Example 18:

(11 ) (13) (14)

(1 1 ) (15) (16)

Compound (13):

A mixture of 0.53 mmol of (11 ), 0.56 mmol of aniline and 0.5 g of molecular sieves is stirred in 3 ml of toluene at room temperature for approximately 20 hours. The mixture is then filtered, the molecular sieves are washed with a small amount of methylene chloride and the solution is concentrated by rotary evaporation. A viscous red oil is obtained in quantitative yield.

Compound (14):

0.24 mmol of (13) is reduced with 1 mmol of lithium aluminium hydride as described for (12).

Purification by chromatography (eluant: EtOH) yields the product in a 90% yield (yellow, solid).

Compounds (15) and (16):

(15) is prepared analogously to (13) with S-2-phenylethylamine and (16) is prepared analogously to (15). Yield (16): 89% (yellow, solid)

Example 19:

Ph,

(12) (19)

0.27 mmol of chloro-diphenylphosphine is added dropwise at 50°C to 0.22 mmol of (12) and 0.34 mmol of triethylamine in 3 ml of toluene. After 2 hours' stirring, the mixture is allowed to cool and the resulting cloudy orange mixture is purified by chromatography (eluant: ethyl acetate/triethylamine 100 :1). The product is obtained in a yield of 52% (yellow-orange, almost solid).

Characteristic NMR signals of compounds (11 ) to (16) and (19):

Comp R ¹ H-NMR (δ) ³¹ P-NMR (δ)

No.

(11) CHO 9.54 (s, 1 H, CHO) - 23.2

(12) CH ₂ OH 3.96 - 4.08 (d of d, 2H, CH ₂ OH) - 22.3

(13) CH=N-Ph 7.92 (s, 1H, CH=N) - 22.6

(14) CH ₂ -NH-Ph 3.52 - 3.67 (d of d, 2H, CH ₂ - ^■ NH) - 22.4

(15) CH=N-CH(CH ₃ )Ph 1.50 (d, 3H, N-CH(CH ₃ )Ph) - 22.5 7.76 (s, 1H, CH=N)

(16) CH ₂ -NH-CH(CH ₃ )Ph 1.26 (d, 3H, N-CH(CH ₃ )Ph) - 22.2

2.9 - 3.16 (d of d, 2H, Chk-NH)

(19) CH ₂ -O-PPh ₂ - 22.2 (cp-PPh ₂ ) + 113.7 (O-PPh ₂ )

Example 20:

(100) (200a)

A solution of 206 mg (0.32 mmol) of (100) in 8 ml of acetic anhydride is stirred at room temperature for 24 hours. The orange solution is then extracted by shaking in aqueous NaCI solution and toluene, and the organic phase is washed with NaCI solution, dried over sodium sulfate and concentrated by rotary evaporation. 210 mg of crude product are obtained (orange almost solid oil), which is reacted further without purification. ¹ H-NMR (CDCI ₃ ) characteristic signals: δ 1.15 (s, C(O)CH ₃ ), 6.19 (m, 1 H, CH(CH ₃ )OAc.

(200a) (200)

0.5 ml of a 1.6M BuLi solution in hexane is added dropwise with stirring at 0°C to a mixture of 200 mg of the crude product (200a) in 10 ml of ether, and the mixture is stirred further for 2.5 hours at 0°C At 0°C, 20 ml of water are then added to the mixture and extraction is carried out with ether. The organic phase is dried with sodium sulfate, concentrated by rotary evaporation and purified by chromatography (silica gel: Merck 60; eluant: ethyl acetate/hexane 1/2). 55 mg of product are obtained (yield 27% based on (100), viscous orange oil).

Analysis:

1H-NMR (CDCI ₃ ) characteristic signals: δ 1.48 (d, 3H, C-CH ₃ ), 3.7-4.5 (m, 7H, C ₅ H ₃ FeC ₅ H ₄ ), 4.95 (m, 1H, CH-CH ₃ ), 7.2-7.6 (m, 10H, P(C ₆ H ₅ ) ₂ . ³ P-NMR (CDCI3): δ -7.1 , -22.9

Application Examples:

Hydroqenation of acetamidocinnamic acid methyl ester:

General: All the operations are carried out under inert gas. The hydrogenations are carried out in a 25 ml glass flask equipped with a magnetic stirrer (1500 rpm), an inert gas connection and a rubber septum. The reactants and the hydrogen are introduced using syringes and needles. All hydrogenations are carried out under normal hydrogen pressure. Procedure: 0.018 mmol of ligand and 0.015 mmol of [Rh(diene) ₂ ]X are dissolved in 3 ml of MeOH in the hydrogenation vessel equipped with a magnetic stirrer and the solution is stirred for 10 minutes. To that catalyst precursor there is then added a solution of 1.5 mmol of acetamidocinnamic acid methyl ester in 7 ml of MeOH. Prior to each hydrogenation the inert gas in the hydrogenation vessel is displaced by hydrogen in 4 cycles (vacuum, normal hydrogen pressure). Hydrogenation is started by switching on the stirrer. The conversion is determined in each case by the consumption of hydrogen or by means of GC (column OV 101 ) and the optical yield is determined by means of GC (column: Chiracil-val). The results are given in the following Table:

Table 4:

Example Ligand Conf. of Rh(diene) ₂ X Conver¬ Time [h] ee Conf. of

No. ligand sion [%] product

30 (111) S.R Rh(COD) ₂ BF 83 6 ^* 44 S

31 (113) S,R Rh(COD) ₂ BF ₄ 98 7 ^* 24 S

32 (15) S.R RH(NBD) ₂ BF ₄ 90 21 16 R

33 (103) R,S Rh(NBD) ₂ BF 83 16 83 R

34 (103) R.S Rh(COD) ₂ BF ₄ 100 0.8 ^* 79 R

35 (102) S,R Rh(COD) ₂ BF ₄ 100 5 76 S

36 (13) S,R Rh(NBD) ₂ BF ₄ 95 24 52 R

37 (14) S,R Rh(NBD) ₂ BF ₄ 66 19 71 R

38 (16) S,R Rh(NBD) ₂ BF 77 25 67 R

39 (17) S.R Rh(NBD) ₂ BF ₄ 88 18 49 R

40 (18) S,R Rh(NBD) ₂ BF ₄ 95 22 62.5 R

Addition of 10 microliters of eSOsH before the hydrogenation

Hydrogenation of keto-pantolactone: catalyst ligand + Rh(l) complex

General: All the operations are carried out under inert gas. The hydrogenations are carried out in a 50 ml steel autoclave equipped with a magnetic stirrer (1500 rpm). The reactants and the hydrogen are introduced using syringes and needles. All hydrogenations are carried out at 50 bar hydrogen pressure.

Procedure: 0.0096 mmol of ligand and 0.008 mmol of Rh(l) complex are dissolved in 3 ml of solvent in a vessel equipped with a magnetic stirrer and the solution is stirred for 10 minutes. The solution is introduced into the autoclave against a current of argon. To that catalyst precursor there is then added a solution of 4 mmol of ketopantolactone in 5 ml of solvent. Prior to each hydrogenation the inert gas in the autoclave is displaced by hydrogen in 4 cycles (vacuum, normal hydrogen pressure). Hydrogenation is started by switching on the stirrer and terminated after 20 hours. The conversion and the optical yield are

determined by means of GC (columns: OV 101 , Lipodex-E). The results are given in the following Table 5:

Table 5:

Ex. No. Ligand R' R" Conf. Rh(l) complex T Sol¬ Conv¬ ee Conf.

°c vent ersion

41 100 Ph Cyh R,S [Rh(COD)CI] ₂ 50 THF 98 77 S

42 101 Ph Cyp R,S [Rh(COD)CI] ₂ 50 THF 100 65 S

43 109 o-Tol Cyh S.R [Rh(COD)CI] ₂ 50 THF 100 72 R

44 109 o-Tol Cyh S,R [Rh(NBD)OAc] ₂ 50 THF 100 75 R

45 109 o-Tol Cyh S,R [Rh(NBD)OAc] ₂ 50 Tol 100 81 R

46 109 o-Tol Cyh S,R [Rh(NBD)OAc] ₂ 25 Tol 100 84 R

47 105 p-PhCF ₃ Cyh R,S [Rh(COD)CI] ₂ 50 THF 95 67 S

48 200 Ph Cyh R,S [Rh(COD)CI] ₂ 50 THF 100 65 S

Y is NMe ₂ in Ex. No. 41 to 47 and Y is OH in Ex. No. 48