Process for an enantioselective catalytic hydrogenation

Abstract

The present invention relates to a process for an enantioselective catalytic hydrogenation of an α,β-unsaturated olefinic double bond of a prochiral α,β-unsaturated carbonyl compound, which comprises subjecting the prochiral α,β-unsaturated carbonyl compound to a homogeneous catalytic hydrogenation in the presence of a chiral catalyst composition, which comprises a first bidentate chiral phosphorus organic ligand (1) having two coordinating phosphorus atoms in the form of diaryl substituted phosphorus atoms, i.e. in the form of diarylphosphine groups P(Ar)2, a second bidentate phosphorus organic ligand (2) having two coordinating phosphorus atoms, where the second bidentate ligand (2) is distinct from the first bidentate chiral ligand, where during the catalytic hydrogenation the molar ratio of the total amount of the ligands (1) and (2) to the rhodium is at least 1.8:1, e. g. in the range of 1.8:1 to 2.5:1, in particular in the range of 1.85:1 to 2.4:1, which generally corresponds to a ratio of P atoms to Rh atoms of at least 3.6:1, e.g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1, where at least in the initial phase of the enantioselective catalytic hydrogenation and preferably throughout the enantioselective catalytic hydrogenation the molar ratio of the ligand (1) to rhodium in the reaction mixture is in the range of 1.0:1 to 1.7:1, in particular in the range of 1.1:1 to 1.6:1. Specifically, the present invention relates to a process for the preparation of optically active aldehydes or ketones, in particular citronellal, by asymmetric hydrogenation of the corresponding prochiral α,β-unsaturated aldehydes or ketones.

Description

[0001] Process for an enantioselective catalytic hydrogenation

[0002] The present invention relates to a process for an enantioselective catalytic hydrogenation of an a,p-unsaturated olefinic double bond of a prochiral a,p-unsaturated carbonyl compound, which comprises subjecting the prochiral a,p-unsaturated carbonyl compound to hydrogen in the presence of a chiral catalyst, which comprises a bidentate chiral phosphorus organic ligand having two coordinating phosphorus atoms in the form of diarylphosphine groups. Specifically, the present invention relates to a process for the preparation of optically active aldehydes or ketones, in particular citronellal, by asymmetric hydrogenation of the corresponding prochiral a,p-unsaturated aldehydes or ketones.

[0003] BACKGROUND OF THE INVENTION

[0004] Many optically active aldehydes and ketones are valuable intermediates in the synthesis of relatively highly refined chiral substances of value and active ingredients, or are already themselves valuable fragrances and aroma substances.

[0005] Chiral Rh-complexes containing rhodium and chiral bisphosphine ligands are used as homogeneous catalysts for the enantioselective hydrogenation of prochiral a,p-unsaturated carbonyl compounds. For example, Rh-complexes prepared from Rh-precursors and a chiral bisphosphine ligand, such as (R,R)-chiraphos, (2R,3R)-2,3-bis(diphenylphosphino)butane, are used for the enantioselective hydrogenation of ciscitral (also called neral). The active catalyst is usually prepared from Rh(CO)2acac and the chiral bisphosphine ligand (see, for example, US20080269528A1 and US2010152494A1). In this process, Rh(CO)2acac and the chiral bisphosphine ligand are reacted under H2 / CO atmosphere to form the active catalyst (for the formation of the active monohydridodicarbonyl-Rh-complex (chiraphos)Rh(CO)2H from Rh(CO)2acac and chiraphos, see e.g. in Jakel et al. Adv. Synth. Catal. 2008, 350, 2708-2714 or in Paciello et al. in Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions, edited by H.-U. Blaser et al., Wiley-VCH, New York, 2010, 187-205).

[0006] One problem when carrying out (homogeneous-catalytic) reactions catalyzed by means of soluble catalysts is the often insufficient stability of the catalyst complexes used or the catalytically active transition metal complex species formed under the reaction conditions. In view of the often high price of such catalysts or catalyst precursors, homogeneous-catalytic reactions with complex transition metal catalysts can only be applied on an industrial scale in an economical manner in specific cases.

[0007] M / BASFTR-2496-PCIn the processes for the asymmetric hydrogenation of a,p-unsaturated carbonyl compounds described in WO 2008 / 132057, the stability and / or the service life of the catalyst complexes was improved by subjecting the catalyst to a preformation in an atmosphere containing carbon monoxide and hydrogen in a specific ratio and carrying out the asymmetric hydrogenation of a,p-unsaturated carbonyl compounds in the presence of small amounts of carbon monoxide. Nevertheless, the process suffers from moderate and fluctuating, often over time declining, catalyst activity, so there is a need for improvement in terms of conversion rates, especially when carried out on an industrial scale.

[0008] US2018057437A1 seeks to overcome the above mentioned problems by addition of diarylphosphine compounds of the formula (I) having a single coordinating phosphorus atom to the asymmetric hydrogenation of prochiral a,p-unsaturated carbonyl compounds. Examples for such diarylphosphine compounds as described in US2018057437A1 either comprise no further phosphorus atom or a non-coordinating phosphorus atom included in phosphine oxide functions in addition to the single coordinating phosphorus atom included in a diarylphosphine group.

[0009] WO 2023 / 137133 describes that a reaction of selective monohydrogenation of dienones with hydrogen in the presence of a single type of rhodium catalysts having diarylphosphine ligands can be performed without the need of certain solvents.

[0010] SUMMARY OF THE INVENTION

[0011] It was surprisingly found that the above problems can be overcome by carrying out the catalytic hydrogenation of an a,p-unsaturated olefinic double bond of a prochiral a,p-unsaturated carbonyl compound in the presence of a chiral catalyst composition comprising a combination of a first bidentate chiral phosphorus organic ligand (1) having two coordinating phosphorus atoms in the form of diaryl substituted phosphine groups P(Ar)2, hereinafter referred to as diarylphosphine groups, and at least one second bidentate phosphorus organic ligand (2) having two coordinating phosphorus atoms, where (L2) is distinct from the first bidentate chiral ligand (L1), where during the catalytic hydrogenation the molar ratio of the total amount of the ligands (1) and (2) to the rhodium is at least 1.8: 1 , e. g. in the range of to 1.8: 1 to 2.5:1, in particular in the range of 1.85:1 to 2.45:1, where at least in the initial phase of the enantioselective catalytic hydrogenation the molar ratio of the ligand (1) to rhodium in the reaction mixture is in the range of 1.0:1 to 1.7:1, in particular in the range of 1.1:1 to 1.6:1.

[0012] It is believed that the decrease of the catalytic activity and selectivity observed when working the prior art is caused by partial degradation of the chiral phosphorus organic ligand. However, the problem could not be overcome by starting with higher ratios of M / BASFTR-2496-PCrhodium to ligand. Rather, higher molar initial ratios of chiral ligand to rhodium of above 1.8:1 or even 1.9:1 or higher for compensating the degradation of the ligand resulted in a further decrease of reactivity and selectivity. The reactivity could be overcome by the combination of the first bidentate chiral phosphorus organic ligand (1) (hereinafter abbreviate as L1) with one or more second bidentate phosphorus organic ligands (2) (hereinafter abbreviate as L2) and comparatively low molar ratios of chiral ligand (1) to rhodium of in the range of 1.0: 1 to 1.7: 1 , in particular in the range of 1.1 : 1 to 1.6:1, preferably while the total amount of the ligands (1) and (2) to the rhodium is at least 1.8:1. Although the at least one second bidentate phosphorus organic ligand (2) is not necessarily chiral and can be achiral, its presence does surprisingly not result in a significantly decreased or even in the absence of enantioselectivity, in particular, if its molar ratio to rhodium does not exceed 1:1 and / or the molar ratio of the total amount of the ligands (1) and (2) to the rhodium does not exceed 2.5:1.

[0013] It is surprising that a catalyst composition having a total molar ratio of ligand (1) plus ligand (2) to Rh [i. e. molar ratio (L1+L2):Rh] of at least 1.8, in particular in the range of (L1+L2):Rh=1.8-2.5, provides a far higher reactivity, and consequently higher turnover rate, compared to the case when the initial molar ratio L1:Rh is 1.9 or higher (and optionally also compared to the case where the molar ratio (L1+L2):Rh is below 1.8, e. g 1.7 or lower). Surprising are in particular the high activities at high molar ratios (L1+L2):Rh. An initial ratio of ligand (1) to rhodium of > 1.7:1, in particular > 1.8:1, e. g. the ratio L1:Rh = 1.9:1, leads to lower activities compared to the case where a portion of the ligand (1) is replaced by the ligand (2), such that that the molar ratio (L1+L2):Rh is > 1.7, e. g. the ratio (L1+L2):Rh = 1.9:1 (with for example L1 = 1.5 and L2 = 0.4), as demonstrated by the examples of the instant application. Therefore, such catalysts provide the desired high Rh-efficiency, such as at a high ratio of (L1+L2):Rh of > 1.8:1.

[0014] Therefore, a first aspect of the present invention relates to a process for an enantioselective catalytic hydrogenation of an a,p-unsaturated olefinic double bond of a prochiral a,p-unsaturated carbonyl compound, which comprises subjecting the prochiral a,p-unsaturated carbonyl compound to a homogeneous catalytic hydrogenation in the presence of a chiral catalyst composition, which comprises rhodium, a first bidentate chiral phosphorus organic ligand (1) having two coordinating phosphorus atoms in the form of diaryl substituted phosphorus atoms, i. e. in the form of diarylphosphine groups P(Ar)2, a second bidentate phosphorus organic ligand (2) having two coordinating phosphorus atoms, where the second bidentate ligand (2) is distinct from the first bidentate chiral ligand, where during the catalytic hydrogenation the molar ratio of the total amount of the ligands (1) and (2) to the rhodium is at least 1.8:1, e. g. in the range of 1.8:1 to 2.5:1, in particular in the range of 1.85:1 to 2.4:1, which generally corresponds to a ratio of P atoms to Rh atoms of at least 3.6:1, e. g. in the range of 3.6: 1 to 5.0: 1 , in particular in the range of 3.7: 1 to 4.8: 1 , where at least in

[0015] M / BASFTR-2496-PCthe initial phase of the enantioselective catalytic hydrogenation and preferably throughout the enantioselective catalytic hydrogenation the molar ratio of the ligand (1) to rhodium in the reaction mixture is in the range of 1.0:1 to 1.7:1, in particular in the range of 1.1:1 to 1.6:1.

[0016] It is clear to a skilled person that the molar ratio of the total amount of the ligands (1) and (2) to rhodium of at least 1.8:1, e. g. in the range of 1.8:1 to 2.5:1, in particular in the range of 1.85:1 to 2.4:1 corresponds to a molar ratio of phosphorus atoms to rhodium atoms, i. e. the molar ratio P:Rh, in the reaction mixture during the enantioselective catalytic hydrogenation of at least 3.6:1, e. g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1. Therefore, the ratio of the total amount of the ligands (1) and (2) can be determined by analyzing the reaction mixture with respect to the ratio of phosphorus atoms to rhodium atoms in the reaction mixture, for example by elemental analysis by inductively coupled plasma mass spectrometry (ICP-MS).

[0017] The process provides for catalytic activity, product selectivity and high enantioselectivity over the time, which renders the process particularly suitable for continuously operated enantioselective catalytic hydrogenation.

[0018] The chiral catalyst composition as described herein are novel and are a second aspect of the present invention. The catalyst composition comprises rhodium, a first bidentate chiral phosphorus organic ligand (1) having two coordinating phosphorus atoms in the form of diaryl substituted phosphorus atoms, i. e. in the form of diarylphosphine groups P(Ar)2, a second bidentate phosphorus organic ligand (2) having two coordinating phosphorus atoms, where the second bidentate ligand (2) is distinct from the first bidentate chiral ligand, wherein the molar ratio of the total amount of the ligands (1) and (2) to the rhodium is at least 1.8:1, e. g. in the range of 1.8:1 to 2.5:1, in particular in the range of 1.85:1 to 2.4:1. In other words, the ratio of P atoms to Rh atoms in the catalyst composition according to the aspect 2 of the present invention is generally at least 3.6:1, e. g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1.

[0019] DETAILED DESCRIPTION OF THE INVENTION

[0020] It will be understood that, as used throughout the present invention, the terms “catalyst composition” and “chiral catalyst composition” may be understood interchangeably. At least ligand (1) preferably is a chiral ligand, thus also a mixture comprising such ligand (1).

[0021] M / BASFTR-2496-PCIt will be understood that, as used throughout the present invention, the terms “ligand (1)” as well as “first bidentate chiral phosphorus organic ligand”, “first bidentate phosphorus organic ligand”, “first bidentate chiral ligand”, and “first ligand” (each optionally with additional indication of number “(1)”) as well as the abbreviation “L1” in the context of ligands may be understood interchangeably.

[0022] It will be understood that, as used throughout the present invention, the terms “ligand (2)” as well as “second bidentate phosphorus organic ligand”, “second bidentate ligand”, and “second ligand” (each optionally with additional indication of number “(2)”) as well as the abbreviation “L2” in the context of ligands may be understood interchangeably.

[0023] It will be understood that the definitions and preferred embodiments as indicated in the context of the processes according to the first aspect of the present invention mutatis mutandis apply to the catalyst composition of the second aspect of the present invention as such. Accordingly, a skilled person will readily understand that the ligand (1) and the ligand (2) comprised in the catalyst composition according to the second aspect of the present invention are each independently from each other defined according to any one of the embodiments as laid out in the context of the processes of the first aspect of the present invention. In particular, a skilled person will readily understand that the preferences with regard to ligands (1) and ligands (2) are the same for the first aspect and the second aspect of the present invention. A skilled person will also readily understand that the preferences with regard to molar ratio of ligand (1) to rhodium and likewise the preferences with regard to molar ratio of ligand (2) to rhodium are the same for the first aspect and the second aspect of the present invention.

[0024] In the definitions of the variables given in the formulae above and below, collective terms are used which are generally representative of the respective substituents. The meaning Cn- to Cm- indicates the respective possible number of carbon atoms in the particular substituents or substituent moiety.

[0025] In the context of the present invention, the expression "alkyl" comprises linear or branched alkyl groups having 1 to 4, 6, 12 or 25 carbon atoms. These include, for example, Ci- to Ce-alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, secbutyl, tert-butyl, n-pentyl, 2-pentyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1.1 -dimethylpropyl, 2,2-dimethylpropyl, 1 -ethylpropyl, n-hexyl, 2-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,3-dimethylbutyl, 1.1 -dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1 , 1 ,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1 -ethylbutyl, 2-ethylbutyl, 1-ethyl-2-methylpropyl and the like.

[0026] Preferably "alkyl" is linear or branched Ci- to Ce-alkyl groups.

[0027] M / BASFTR-2496-PCIn the context of the present invention, the expression "cycloalkyl" comprises cyclic, saturated hydrocarbon groups having 3 to 6, 12 or 25 carbon ring members, e.g. Ca-Cs-cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, or C7-Ci2-bicycloalkyl. Herein, cycloalkyl is also abbreviated as c-alkyl.

[0028] In the context of the present invention, the expression "alkoxy" is an alkyl group having 1 to 6 carbon atoms bonded via an oxygen, e.g. Ci- to Ce-alkoxy, such as methoxy, ethoxy, n-propoxy, 1 -methylethoxy, butoxy, 1 -methylpropoxy, 2-methylpropoxy, 1.1 -dimethylethoxy, pentoxy, 1 -methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1.1 -dimethylpropoxy, 1 ,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1 -ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1.1 -dimethylbutoxy, 1 ,2-dimethylbutoxy, 1 ,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1 -ethylbutoxy, 2-ethylbutoxy, 1 , 1 ,2-trimethyl-propoxy, 1,2,2-trimethylpropoxy, 1 -ethyl- 1 -methylpropoxy or 1-ethyl-2-methylpropoxy. Preferably, "alkoxy" is Ci- to C4-alkoxy.

[0029] In the context of the present invention, the term “5, 6 or 7 membered carbocyclic group” refers to a saturated or unsaturated monocyclic, non-aromatic or aromatic hydrocarbon group with 5, 6 or 7 carbon atoms. These include, for example, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl and benzyl.

[0030] In the context of the present invention, the term “6, 7 or 8 membered carbobicyclic group” refers to saturated or unsaturated bicyclic hydrocarbon group with 6, 7 or 8 carbon atoms. These include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.1]heptenyl, bicyclo[2.1.1]hexanyl and bicyclo[2.2.2]octyl.

[0031] In the context of the present invention, the term “5, 6 or 7 membered heterocyclic group” refers to a saturated or unsaturated, non-aromatic or aromatic ring or ring system containing 3 to 6 carbon atoms and at least one heteroatom selected from O, S and N. Suitable non-aromatic heterocyclic groups include e.g. tetrahydrofuranyl, dihydrofuranyl, 1,4-dioxanyl, morpholinyl, 1 ,4-dithianyl, piperazinyl, piperidinyl, 1,3-dioxolanyl, imidazolidinyl, imidazolinyl, pyrrolinyl, pyrrolidinyl, tetrahydropyranyl, dihydropyranyl, oxathiolanyl, dithiolanyl, 1,3-dioxanyl, 1 ,3-dithianyl, oxathianyl, thiazolidinyl and thiomorpholinyl. Suitable aromatic heterocyclic groups include e.g. 2-or 3-thienyl, 2- or 3-furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, 2-, 3-, or 4-pyridyl, pyridazinyl, pyrazinyl and pyrimidinyl.

[0032] In the context of the present invention, the expression "C1-C4 alkanolate" refers to the conjugate base of the corresponding C1-C4 alkanol. These include, for example,

[0033] M / BASFTR-2496-PCmethanolate, ethanolate, propanolate, butanolate, isopropanolate, tert-butanolate and isobutanolate.

[0034] In the context of the present invention, the expression "C1-C4 alkanoate" refers to the conjugate base of the corresponding C1-C4 alkanoic acid. These include, for example, formate, acetate, propanoate, butanoate, isopropanoate, tert-butanoate and isobutanoate.

[0035] In the context of the present invention, the expression "alkenyl" comprises linear or branched hydrocarbon radicals having 2 to 4, 6, 12 or 25 carbon atoms which comprise at least one double bond, for example 1 , 2, 3 or 4 double bonds. These include, for example, C2-Ce-alkenyl such as ethenyl, 1 -propenyl, 2-propenyl, 1 -methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,

[0036] 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1 propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1 -pentenyl, 4-methyl-1 -pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1 -propenyl and 1-ethyl-2-methyl-2-propenyl.

[0037] Preferably, "alkenyl" is linear C2- to Ci2-alkenyl groups or branched C3- to Ci2-alkenyl groups having in each case 1 to 3 double bonds, particularly preferably linear C2- to Ce-alkenyl groups or branched C3- to Ce-alkenyl groups having in each case one double bond.

[0038] In the context of the present invention, the expression "alkylene" refers to divalent hydrocarbon radicals having 2 to 25 carbon atoms. The divalent hydrocarbon radicals can be linear or branched. These include, for example, C2-Ci6-alkylene groups, such as 1.4-butylene, 1,5-pentylene, 2-methyl-1,4-butylene, 1,6-hexylene, 2-methyl- 1.5-pentylene, 3-methyl-1,5-pentylene, 1,7-heptylene, 2-methyl-1,6-hexylene, 3-methyl- 1.6-hexylene, 2-ethyl-1,5-pentylene, 3-ethyl-1,5-pentylene, 2,3-dimethyl-1,5-pentylene, 2,4-dimethyl-1,5-pentylene, 1,8-octylene, 2-methyl-1,7-heptylene, 3-methyl-

[0039] M / BASFTR-2496-PC1.7-heptylene, 4-methyl-1,7-heptylene, 2-ethyl-1,6-hexylene, 3-ethyl-1,6-hexylene, 2,3-dimethyl-1,6-hexylene, 2,4-dimethyl-1,6-hexylene, 1,9-nonylene, 2-methyl- 1.8-octylene, 3-methyl-1,8-octylene, 4-methyl-1,8-octylene, 2-ethyl-1,7-heptylene, 3-ethyl-1,7-heptylene, 1,10-decylene, 2-methyl-1,9-nonylene, 3-methyl-1,9-nonylene, 4-methyl-1,9-nonylene, 5-methyl-1,9-nonylene, 1,11-undecylene, 2-methyl-1,10-decylene, 3-methyl-1,10-decylene, 5-methyl-1,10-decylene, 1,12-dodecylene, 1,13-tridecylene, 1,14-tetradecylene, 1,15-pentadecylene, 1,16-hexadecylene and the like. Preferably, "alkylene" is linear C2- to Ci2-alkylene groups or branched C3- to C12-alkylene groups, in particular linear C2- to Ce-alkylene groups or branched C3- to Ce-alkylene groups.

[0040] In the mono- or polybranched or substituted alkylene groups, the carbon atom at the branching point or the carbon atoms at the respective branching points or the carbon atoms carrying a substituent can have, independently of one another, a R or S configuration or both configurations in equal or different proportions.

[0041] In the context of the present invention, the expression "alkenylene" refers to divalent hydrocarbon radicals having 2 to 25 carbon atoms, which can be linear or branched, where the main chain has one or more double bonds, for example 1, 2 or 3 double bonds. These include, for example, C2- to Cis-alkenylene groups, such as ethylene, propylene, 1-, 2-butylene, 1-, 2-pentylene, 1-, 2-, 3-hexylene, 1,3-hexadienylene, 1,4-hexadienylene, 1-, 2-, 3-heptylene, 1,3-heptadienylene, 1,4-heptydienylene, 2,4-heptadienylene, 1-, 2-, 3-octenylene, 1,3-octadienylene, 1 ,4-octadienylene, 2,4-octadienylene, 1-, 2-, 3-nonenylene, 1-, 2-, 3-, 4-, 5-decenylene, 1-, 2-, 3-, 4-,

[0042] 5-undecenylene, 2-, 3-, 4-, 5-, 6-dodecenylene, 2,4-dodecadienylene,

[0043] 2.5-dodecadienylene, 2,6-dodecadienylene, 3-, 4-, 5-, 6-tridecenylene,

[0044] 2.5-tridecadienylene, 4,7-tridecadienylene, 5,8-tridecadienylene, 4-, 5-, 6-,

[0045] 7-tetradecenylene, 2,5-tetradecadienylene, 4,7-tetradecadienylene,

[0046] 5,8-tetradecadienylene, 4-, 5-, 6-, 7-pentadecenylene, 2,5-pentadecadienylene, 4.7-pentadecadienylene, 5,8-pentadecadienylene, 1 ,4,7-pentadecatrienylene, 4,7,11-pentadecatrienylene, 4,6,8-pentadecatrienylene, 4-, 5-, 6-, 7-,

[0047] 8-hexadecenylene, 2,5-hexadecadienylene, 4,7-hexadecadienylene,

[0048] 5.8-hexadecadienylene, 2,5,8-hexadecatrienylene, 4,8,11-hexadecatrienylene, 5,7,9-hexadecatrienylene, 5-, 6-, 7-, 8-heptadecenylene, 2,5-heptadecadienylene, 4,7-heptadecadienylene, 5,8-heptadecadienylene, 5-, 6-, 7-, 8-, 9-octadecenylene, 2.5-octadecadienylene, 4,7-octadecadienylene, 5,8-octadecadienylene and the like. Preferably, "alkenylene" is linear C3- to Ci2-alkenylene groups or branched C4- to C12-alkenylene groups having in each case one or two double bonds, in particular linear Cato Cs-alkenylene groups with one double bond.

[0049] M / BASFTR-2496-PCThe double bonds in the alkenylene groups can be present independently of one another in the E and also in the Z configuration or as a mixture of both configurations.

[0050] In the context of the present invention, the expression "halogen" comprises fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine or bromine.

[0051] In the context of the present invention, the expression "aryl" comprises a mono- to trinuclear aromatic ring system comprising 6 to 14 carbon ring members. These include, for example, Ce- to Cw-aryl, such as phenyl or naphthyl.

[0052] In the context of the present invention, the expression "hetaryl" comprises mono- to trinuclear aromatic ring system comprising 6 to 14 carbon ring members, where one or more, for example 1, 2, 3, 4, 5 or 6, carbon atoms are substituted by a nitrogen, oxygen and / or sulfur atom. These include, for example, C3- to Ce-hetaryl groups, such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1 ,2,4-thiadiazol- 3-yl, 1 ,2,4-thiadiazol-5-yl, 1 ,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-yl, 1 ,3,4-thiadiazol-2-yl, 1 ,3,4-triazol-2-yl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1 ,3,5-triazin-2-yl, 1 ,2,4-triazin-3-yl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl and the like. Preferably, "hetaryl" is C5- to Ce-hetaryl.

[0053] In the context of the present invention, the expression "aralkyl" comprises a mono- to dinuclear aromatic ring system, comprising 6 to 10 carbon ring members, bonded via an linear or branched Ci- to Ce-alkyl group. These include, for example, C7- to C12-aralkyl, such as phenylmethyl, 1 -phenylethyl, 2-phenylethyl, 1-phenylpropyl,

[0054] 2-phenylpropyl, 3-phenylpropyl and the like.

[0055] In the context of the present invention, the expression "alkylaryl" comprises mono- to dinuclear aromatic ring systems comprising 6 to 10 carbon ring members which are substituted with one or more, for example 1, 2 or 3, linear or branched Ci- to Ce-alkyl radicals. These include e.g. C7- to Ci2-alkylaryl, such as 1 -methylphenyl, 2-methyl-phenyl, 3-methylphenyl, 1 -ethylphenyl, 2-ethylphenyl, 3-ethylphenyl, 1 -propylphenyl, 2-propylphenyl, 3-propylphenyl, 1 -isopropylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 1-butylphenyl, 2-butylphenyl, 3-butylphenyl, 1 -isobutylphenyl, 2-isobutylphenyl, 3-iso-butylphenyl, 1-sec-butylphenyl, 2-sec-butylphenyl, 3-sec-butylphenyl, 1-tert-butylphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 1-(1-pentenyl) phenyl, 2-(1-pentenyl)phenyl, 3-(1-pentenyl)phenyl, 1-(2-pentenyl)phenyl, 2-(2-pentenyl)phenyl, 3-(2-pentenyl)phenyl, 1-(3-pentenyl)phenyl, 2-(3-pentenyl)phenyl, 3-(3-pentenyl)phenyl,

[0056] M / BASFTR-2496-PC1-(1-(2-methylbutyl))phenyl, 2-(1-(2-methylbutyl))phenyl, 3-(1-(2-methylbutyl))phenyl, 1-(2-(2-methylbutyl))phenyl, 2-(2-(2-methylbutyl))phenyl, 3-(2-(2-methylbutyl))phenyl, 1-(3-(2-methylbutyl))phenyl, 2-(3-(2-methylbutyl))phenyl, 3-(3-(2-methylbutyl))phenyl, 1-(4-(2-methylbutyl))phenyl, 2-(4-(2-methylbutyl))phenyl, 3-(4-(2-methylbutyl))phenyl, 1-(1-(2,2-dimethylpropyl))phenyl, 2-(1-(2,2-dimethylpropyl))phenyl, 3-(1-(2,2-dimethylpropyl))phenyl, 1-(1-hexenyl)phenyl, 2-(1-hexenyl)phenyl, 3-(1-hexenyl)phenyl, 1-(2-hexenyl)phenyl, 2-(2-hexenyl)phenyl, 3-(2-hexenyl)phenyl, 1-(3-hexenyl)phenyl, 2-(3-hexenyl)phenyl, 3-(3-hexenyl)phenyl, 1-(1-(2-methylpentenyl))phenyl, 2-(1-(2-methylpentenyl))phenyl, 3-(1-(2-methylpentenyl))phenyl, 1-(2-(2-methyl-pentenyl))phenyl, 2-(2-(2-methylpentenyl))phenyl, 3-(2-(2-methylpentenyl))phenyl, 1-(3-(2-methylpentenyl))phenyl, 2-(3-(2-methylpentenyl))phenyl, 3-(3-(2-methylpentenyl)) phenyl, 1-(4-(2-methylpentenyl))phenyl, 2-(4-(2-methylpentenyl))phenyl, 3-(4-(2-methyl-pentenyl))phenyl, 1-(5-(2-methylpentenyl))phenyl, 2-(5-(2-methylpentenyl))phenyl, 3-(5-(2-methylpentenyl))phenyl, 1-(1-(2,2-dimethylbutenyl))phenyl, 2-(1-(2,2-dimethyl-butenyl))phenyl, 3-(1-(2,2-dimethylbutenyl))phenyl, 1-(3-(2,2-dimethylbutenyl))phenyl, 2-(3-(2,2-dimethylbutenyl))phenyl, 3-(3-(2,2-dimethylbutenyl))phenyl, 1-(4-(2,2-dimethylbutenyl))phenyl, 2-(4-(2,2-dimethylbutenyl))phenyl, 3-(4-(2,2-dimethylbutenyl)) phenyl and the like.

[0057] The term “bidentate phosphorus organic ligand” as used herein refers to a compound which has two phosphorus atoms that are capable of coordinating the rhodium atom. Each of these phosphorus atoms have a lone pair on the coordinating phosphorus atom. The term “lone pair” is understood to refer to a pair of valence electrons that are not shared with another atoms in a covalent bond. The term “lone pair” is sometimes called “unshared pair” or “non-bonding pair”. Typically, the coordinating phosphorus atoms have 3 P-C bonds or 2 P-C bonds and a P-H bond. In a preferred embodiment, each coordinating phosphorus atom forms part of a phosphine group. Moieties, where the phosphorus atom is oxidized, i. e. is a P=O group, are not capable of coordinating the rhodium atom. In groups where the phosphorus atom is present as a P=O group, the lone pair is no longer present, but replaced by an oxygen atom. Hence compounds derived from bidentate ligands, wherein one or both of the phosphorus atoms are oxidized are not envisaged as ligands (1) and (2).

[0058] In the context of the present invention, the expression "at least one ligand (2)" includes a single ligand (2) and combinations of at least 2 ligands (2), e. g. 2, 3, 4, 5 or 6 different ligands (2).

[0059] The remarks made below concerning preferred embodiments of the variables (substituents) are valid on their own as well as preferably in combination with each other. These combinations concern the process parameters, the chiral bidentate

[0060] M / BASFTR-2496-PCligands (1), the at least one second bidentate ligand (2), as well as their ratios concerning the uses according to the invention.

[0061] According to the invention, the enantioselective catalytic hydrogenation is carried out in the presence of a chiral catalyst composition which is dissolved in the reaction mixture (homogeneous catalytic hydrogenation). According to the invention the catalyst composition comprises rhodium, a first bidentate chiral phosphorus organic ligand (1) and at least a second bidentate phosphorus organic ligand (2), e. g. 1, 2, 3, 4, 5 or 6 ligands (2) which is / are different from the first bidentate chiral phosphorus organic ligand (1). It is apparent from the above explanations, that in the initial phase of the enantioselective catalytic hydrogenation the first bidentate chiral phosphorus organic ligand (1) provides sufficient catalytic activity. Consequently, the process of the present invention comprises embodiments, where in the in the initial phase only the first bidentate chiral phosphorus organic ligand (1) and, of course, rhodium are present in the reaction mixture, while the at least one second bidentate phosphorus organic ligand (2) is present at a later time, i. e. after the initial phase, of the enantioselective catalytic hydrogenation.

[0062] The initial phase is understood as the time period starting at the beginning of a continuously operated enantioselective catalytic hydrogenation and lasting as long as the turnover rate of the enantioselective hydrogenation does not decrease more than 10%, based on the starting turnover rate. The turnover rate here is the turnover rate of the starting material, i. e. the unsaturated aldehyde or ketone, e. g. citral, with respect to the concentration of rhodium in the reaction mixture. The initial phase may as an example last 1d to 100d or 7d to 30d depending on the reaction conditions and reactivity and can be (easily) monitored.

[0063] According to the first aspect of the present invention, the molar ratio of the first bidentate chiral phosphorus organic ligand (1) to rhodium is in the range of 1.0:1 to 1.7:1, in particular in the range of 1.1:1 to 1.6:1 at least in the initial phase of the enantioselective catalytic hydrogenation, and preferably throughout the enantioselective catalytic hydrogenation, while the total amount of the ligands (1) and (2) to the rhodium is at least 1.8:1, e. g. in the range of 1.8:1 to 2.5:1 , in particular in the range of 1.85:1 to 2.4:1 during the enantioselective catalytic hydrogenation, which corresponds to a molar ratio P:Rh in the reaction mixture of at least 3.6:1, e. g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1 during the enantioselective catalytic hydrogenation.

[0064] Accordingly, in the catalyst compositions of the second aspect of the present invention, the molar ratio of the first bidentate chiral phosphorus organic ligand (1) to rhodium is generally in the range of 1.0: 1 to 1.7: 1 , in particular in the range of 1.1 : 1 to 1.6: 1.

[0065] M / BASFTR-2496-PCPreferably, the catalyst composition of the second aspect of the present invention is further characterized in that the molar ratio of P atoms to Rh atoms is at least 3.6:1, e. g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1.

[0066] In a preferred embodiment of the catalyst composition according to the second invention, the molar ratio of ligand (2) to rhodium does not exceed 1:1 and / or wherein ligand (2) comprises two phosphine groups. In particular the molar ratio of the first bidentate chiral phosphorus organic ligand (1) to rhodium is generally in the range of 1.0:1 to 1.7:1, in particular in the range of 1.1:1 to 1.6:1, and the molar ratio of ligand (2) to rhodium does not exceed 1:1 and / or the ligand (2) comprises two phosphine groups.

[0067] A distinction is made here between a catalyst composition which can be analyzed, for example by elemental analysis, in any situation which is the result of a protocol, e.g. a continuously operated hydrogenation which starts with an initial composition which is later modified by addition of L1 and / or L2 and / or Rh precursors over time, and an initial situation in which an initial catalyst composition is used. The initial catalyst composition can, but does not necessarily have to, correspond to the catalyst composition according to the invention. Rather, the initial catalyst composition can modified by the adjusting the amount of rhodium and / or the ligands L1 and L2 in the course of the reaction so that it corresponds to the catalyst composition according to the claim after the initial phase. Optionally, in one embodiment, the ratio (L1+L2):Rh in the initial phase can be below 1.8:1.0. In another embodiment, the ratio (L1+L2):Rh in the initial phase can be at least 1.8:1.0. In any case, the catalyst composition present in the initial reaction mixture should have a molar ratio of ligand (1) to rhodium in the range of 1.0:1 to 1.7:1.

[0068] During the catalytic hydrogenation, in particular during a continuously operated enantioselective catalytic hydrogenation, the ratio of the total amount of ligand (1) and ligand (2) to rhodium is generally maintained in the reaction mixture to be at least 1.8:1, preferably in the range from 1.8:1 to 2.5:1, in particular in the range of 1.85 to 2.4, by addition of ligand (1) and / or the ligand (2) into the reaction mixture. In other words, a molar ratio P:Rh is generally maintained in the reaction mixture to be at least 3.6:1, e. g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1 during the enantioselective catalytic hydrogenation.

[0069] In particular in a continuously operated enantioselective catalytic hydrogenation, the molar ratio of the ligand (1) to the rhodium is maintained in the range of 1.0:1 to 1.7:1, in particular in the range of 1.1:1 to 1.6:1. The maintenance of said ratio can be achieved by dosing further ligand (1) into the reaction mixture, such that the molar ratio of the total amount of the ligands (1) and (2) to the rhodium is at least 1.8:1, e. g. in the

[0070] M / BASFTR-2496-PCrange of 1.8: 1 to 2.5: 1 , in particular in the range of 1.85: 1 to 2.4: 1 or that the molar ratio P:Rh is at least 3.6:1, e. g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1. The dosing can be carried out by introducing the ligand (1) into the reaction mixture, which can be done in portions or continuously. The loss of ligand (L1) can be monitored by determining the actual content of the ligand (1) in the reaction mixture.

[0071] It is also clear from the foregoing that the total amount of the ligands (1) and (2) of at least 1.8:1, e. g. in the range of 1.8:1 to 2.5:1, in particular in the range of 1.85:1 to 2.4:1 or the molar ratio P:Rh of at least 3.6:1, e. g. in the range of 3.6:1 to 5.0:1, in particular in the range of 3.7:1 to 4.8:1, respectively, is not necessarily fulfilled during the initial phase but throughout the period of the enantioselective catalytic hydrogenation immediately after the initial period.

[0072] According to the invention, the first bidentate chiral phosphorus organic ligand (1) is chiral and has two coordinating phosphorus atoms in the form of diaryl substituted phosphine groups. A diaryl substituted phosphine group refers to a trivalent phosphorus atom which bears 2 aryl groups, i. e. groups -P(Ar)2, where Ar is an aryl group as defined herein.

[0073] Typically, the first bidentate chiral phosphorus organic ligand (1) has at least one asymmetric carbon atom and preferably at least 2 asymmetric carbon atoms and bears at least 2 diarylphosphine groups that are bound to carbon atoms of a divalent organic radical, in particular a divalent alkyl group, a divalent cycloalkyl group, a divalent bicycloalkyl group, a divalent bicycloalkenyl group or a divalent heterocycloalkyl group.

[0074] In particular, the asymmetric carbon atoms are those which bear the coordinating phosphorus atoms of the ligand, i. e. the diarylphosphine groups -P(Ar)2. Typically, the aryl groups Ar of the diarylphosphine groups in the ligand (1) and, likewise any aryl in any aryl substituted phosphine group in the ligand (2) are, Ce-C -aryl, such as phenyl or naphthyl, which is unsubstituted or carries one or more, e. g. 1, 2 or 3 substituents which are selected from the group of Ci-Ce-alkyl, Cs-Ce-cycloalkyl, phenyl, Ci-Ce-alkoxy, phenoxy and amino, and in particular from the group of Ci-C4-alkyl, Cs-Ce-cycloalkyl, phenyl and Ci-C4-alkoxy. Preferably, the aryl group on the phosphorus atoms in the ligands (1) and (2) are selected from phenyl, which is unsubstituted, and phenyl, which carries 1, 2 or 3 substituents, which are selected from the group consisting of Ci-Ce-alkyl, Cs-Ce-cycloalkyl, phenyl, Ci-Ce-alkoxy, phenoxy and amino, and in particular from the group of Ci-C4-alkyl, Cs-Ce-cycloalkyl, phenyl and C1-C4-alkoxy. More preferably, the aryl groups Ar on the phosphorus atoms of the phosphine groups in the ligands (1) and (2) are selected from phenyl, which is unsubstituted, and phenyl, which carries 1, 2 or 3 substituents, which are selected from the group

[0075] M / BASFTR-2496-PCconsisting of methyl, ethyl, n-propyl, n-butyl, tert.-butyl, cyclohexyl, methoxy and ethoxy. Especially, the aryl group on the phosphorus atoms in the ligands (1) and (2) are phenyl, which is unsubstituted.

[0076] Preferably, the first bidentate phosphorus organic ligand (1) in the first and the second aspect of the present invention is a chiral compound of the formula (1):

[0077] Ar— P P— Ar

[0078] I I

[0079] Ar Ar

[0080]

[0081] (1)

[0082] where

[0083] Rais selected from the group consisting of Ci-Ce-alkyl and Cs-Ce-cycloalkyl, preferably is Ci-Cs-alkyl, and in particular is methyl;

[0084] Rbis selected from the group consisting of hydrogen and Ci-Ce-alkyl, preferably is Ci-Cs-alkyl, more preferably is hydrogen or methyl, and in particular is methyl; or

[0085] Ra, Rbtogether with the carbon atoms, to which they are bound form a 5, 6 or 7 membered carbocyclic group, a 6, 7 or 8 membered carbobicyclic group or a 5, 6 or 7 membered heterocyclic group, where the carbocyclic group, the carbobicyclic group and the heterocyclic group are unsubstituted or substituted by 1, 2, 3 or 4 substituents Rcyc, which are selected from Ci-Ce-alkyl, phenyl and benzyl; where Raand Rb, together with the carbon atoms to which they are bonded, are preferably 1,2-cyclopentylene, 1,2-cyclohexylene, bicyclo[2.2.1]heptylene, in particular 2,3-bicyclo[2.2.1]heptylene, bicyclo[2.2.1]heptenylene, in particular 2,3-bicyclo[2.2.1]heptenylene, bicyclo[2.1.1]hexylene, in particular 2, 3-bicyclo[2.1.1 ]hexylene, bicyclo[2.2.2]octylene, in particular 2, 3-bicyclo[2.2.2]octylene, tetrahydrofuranylene, e. g. 3,4-tetrahydrofuranylene, pyrrolidinylene, e. g. 3,4- pyrrolidinylene, tetrahydropyranylene and morpholinylene, in particular 1,2- cyclohexylene, 2,3-bicyclo[2.2.1]heptenylene and N-benzyl-pyrrolidin-3,4-diyl;

[0086] Ar are identical or different and selected from the group consisting of Ce-Cw-aryl, such as phenyl or naphthyl, where Ce-Cw-aryl is unsubstituted or carries one or more, e. g. 1, 2 or 3, substituents which are selected from Ci-Ce-alkyl, C3-C6- cycloalkyl, phenyl, Ci-Ce-alkoxy, phenoxy and amino, where the substituents are in particular selected from the group of Ci-C4-alkyl, Cs-Ce-cycloalkyl, phenyl and Ci-C4-alkoxy. More preferably, the Ar is selected from phenyl, which is

[0087] M / BASFTR-2496-PCunsubstituted, and phenyl, which carries 1, 2 or 3 substituents, which are selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, tert.-butyl, cyclohexyl, methoxy and ethoxy. Especially, Ar is phenyl, which is unsubstituted.

[0088] The two carbon atoms in formula (1) to which the radicals Raand Rbare bonded can both have a (R) or (S) configuration. The compounds of the formula (1) are chiral, i. e. the carbon atoms bearing the radicals Raand Rbhave either both (R) configuration or (S) configuration. Thus, the compound of formula (1) can be present as the pure (R,R)-or the pure (S,S)-enantiomer.

[0089] Here and in the following, a pure stereoisomer is understood as meaning chiral substances which, with regard to the desired stereoisomer, have an enantiomeric excess (ee) of at least 80% ee, in particular at least 90% ee and specifically at least 95% ee.

[0090] Within the above preferred group of embodiments of the first and second aspects of the present invention particular preference is given to bidentate phosphorus organic ligand (1) which are selected from the group consisting of compounds of the formulae (1a) to (1d) and the enantiomers thereof:

[0091] (1-a) (1-b) (1-c)

[0092]

[0093] (1-d)

[0094] In this context even more preference is given to the ligand (1) of the formula (1-a) and its enantiomer, i.e. to the compounds (2R, 3R)-(+)-bis(diphenylphosphino)butane (also called herein (R,R)-chiraphos) and (2S, 3S)-(-)-bis(diphenylphosphino)butane (also called herein (S,S)-chiraphos).

[0095] M / BASFTR-2496-PCThe bidentate phosphorus organic ligands (1), in particular the ligands of formula (1), are preferably present in enantiopure form and in particular have an enantiomeric excess of at least 90% ee, especially at least 95% ee.

[0096] The at least one second bidentate phosphorus organic ligand (2) is distinct from the first bidentate phosphorus organic ligand (1). According to the first aspect and the second aspect of the present invention, the second bidentate ligand (2) has two coordinating phosphorus atoms. The two coordinating phosphorus atoms may be any phosphorus atoms that enable coordination with one or more transition metals such as rhodium. As explained above, the phosphorus atoms in the bidentate ligands (1) and (2) have a lone pair on each of the phosphorus atoms. In a preferred embodiment, each coordinating phosphorus atom forms part of a phosphine group. In particular, any bidentate phosphorus organic ligand (2) is distinct from the bidentate phosphorus organic ligand (1) by its substitution pattern on the phosphorus atoms or by being an achiral bidentate phosphorus organic ligand. For example, a distinction by the substitution pattern may be that at least one of the coordinating phosphorus atoms of the at least one bidentate phosphorus organic ligand (2) contains only a single aryl group and instead of a second aryl group a hydrogen atom or a non-aryl group, such as an alkyl group having e. g. 1 to 10 carbon atoms or a cycloalkyl group having e. g. 5 to 10 carbon atoms, such as cyclohexyl, which is unsubstituted or carries 1 , 2 or 3 radicals selected from the group of Ci-C4-alkyl, Cs-Ce-cycloalkyl, phenyl and C1-C4-alkoxy. The at least one bidentate phosphorus organic ligand (2) may also be distinct from the bidentate phosphorus organic ligand (1) that it is achiral. It is also apparent that the second bidentate phosphorus organic ligand (2) can be distinct from the first bidentate phosphorus organic ligand (1) by having a smaller number of asymmetric carbon atoms than ligand (1). For example, if the first bidentate phosphorus organic ligand (1) has 2 asymmetric carbon atoms, the second bidentate phosphorus organic ligand (2) may be a chiral but has only 1 asymmetric carbon atom.

[0097] Preferably, the at least one second bidentate phosphorus organic ligand (2) is selected from achiral bidentate ligands having two diarylphosphine groups P(Ar)2, chiral bidentate ligands having two diarylphosphine groups P(Ar)2 and 1 asymmetric carbon atom, achiral bidentate ligands having 1 or 2 monoaryl substituted phosphorus atoms, i. e. monoarylphosphine groups PH(Ar), and optionally 1 diarylphosphine group P(Ar)2, chiral bidentate ligands having at least one monoarylphosphine groups PH(Ar), and optionally 1 diarylphosphine group P(Ar)2, achiral bidentate ligands having 1 or 2 phosphorus atoms bearing an aryl and a cycloalkyl group, i. e. arylcycloalkylphosphine groups P(c-alkyl)(Ar) and optionally 1 diarylphosphine group P(Ar)2, chiral bidentate ligands having 1 or 2 arylcycloalkylphosphine groups P(c-alkyl)(Ar) and optionally 1 diarylphosphine group P(Ar)2, and mixtures thereof.

[0098] M / BASFTR-2496-PCIn particular, achiral compounds which are suitable as phosphorus organic ligands (2) according to the first and the second aspects of the present invention may be organic compounds bearing two groups (Ar’)2P, which are linked by a carbon linker, which has no center of asymmetry, or which has 2 asymmetric carbon atoms but is a meso-form.

[0099] In particular, compounds, which are suitable as phosphorus organic ligands (2) can be described by the formula (2):

[0100]

[0101] k is 0 or 1 ,

[0102] R1is selected from the group consisting of hydrogen, Ci-Ce-alkyl and C3-C6- cycloalkyl, preferably is hydrogen, Ci-Cs-alkyl, and in particular is hydrogen or methyl;

[0103] R2is selected from the group consisting of hydrogen, Ci-Ce-alkyl and C3-C6- cycloalkyl, preferably is hydrogen, Ci-Cs-alkyl, and in particular is hydrogen or methyl;

[0104] or, if k = 0,

[0105] R1, R2together with the carbon atoms, to which they are bound may form a 5, 6 or 7 membered carbocyclic group, a 6, 7 or 8 membered carbobicyclic group or a 5, 6 or 7 membered heterocyclic group, where the carbocyclic group, the carbobicyclic group and the heterocyclic group are unsubstituted or substituted by 1, 2, 3 or 4 substituents Rcyc, which are selected from Ci-Ce-alkyl, phenyl and benzyl; where R1and R2, together with the carbon atoms to which they are bonded, are preferably 1,2-cyclopentylene, 1,2-cyclohexylene, bicyclo[2.2.1]heptylene, in particular 2,3-bicyclo[2.2.1]heptylene, bicyclo[2.2.1]heptenylene, in particular 2,3-bicyclo[2.2.1]heptenylene, bicyclo[2.1.1]hexylene, in particular 2, 3-bicyclo[2.1.1 ]hexylene, bicyclo[2.2.2]octylene, in particular 2, 3-bicyclo[2.2.2]octylene, tetrahydrofuranylene, e. g. 3,4-tetrahydrofuranylene, pyrrolidinylene, e. g. 3,4- pyrrolidinylene, tetrahydropyranylene and morpholinylene, in particular 1,2- cyclohexylene, 2,3-bicyclo[2.2.1]heptenylene and N-benzyl-pyrrolidin-3,4-diyl;

[0106] Ar’ are identical or different and selected from the group consisting of Ce-C -aryl, such as phenyl or naphthyl, where Ce-Cw-aryl is unsubstituted or carries one or more, e. g. 1, 2 or 3, substituents which are selected from Ci-Ce-alkyl, C3-C6- cycloalkyl, phenyl, Ci-Ce-alkoxy, phenoxy and amino, where the substituents are M / BASFTR-2496-PCin particular selected from the group of Ci-C4-alkyl, Cs-Cs-cycloalkyl, phenyl and Ci-C4-alkoxy. More preferably, the Ar’ is selected from phenyl, which is unsubstituted, and phenyl, which carries 1, 2 or 3 substituents, which are selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, tert.-butyl, cyclohexyl, methoxy and ethoxy. Especially, Ar’ is phenyl, which is unsubstituted.

[0107] R3, R4which are identical or different and selected from the group consisting of hydrogen, Cs-Cw-cycloalkyl, such as cyclopentyl or cyclohexyl, Ce-Cw-aryl, such as phenyl or naphthyl, where Cs-Cw-cycloalkyl and Cs-Cw-aryl are unsubstituted or carries one or more, e. g. 1, 2 or 3, substituents which are selected from Ci-Cs-alkyl, Cs-Cs-cycloalkyl, phenyl, Ci-Cs-alkoxy, phenoxy and amino, where the substituents are in particular selected from the group of Ci-C4-alkyl, Cs-Cs- cycloalkyl, phenyl and Ci-C4-alkoxy. More preferably, the R3, R4are selected from hydrogen, cyclohexyl or phenyl, which are unsubstituted, and cyclohexyl or phenyl, which carry 1, 2 or 3 substituents, which are selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, tert.-butyl, cyclohexyl, methoxy and ethoxy. Especially, R3, R4are selected from hydrogen, cyclohexyl and phenyl, where cyclohexyl and phenyl are unsubstituted;

[0108] provided that in formula (2) at least one of the following conditions (a)-(d) are met:

[0109] (a) both R1and R2are hydrogen;

[0110] (b) k is 1;

[0111] (c) if both R1and R2are different from hydrogen, the compound of formula (2) is achiral, because R1and R2are identical or together with the carbon atoms, to which they are bound may form a symmetric 5, 6 or 7 membered carbocyclic group, a symmetric 6, 7 or 8 membered carbobicyclic group or a symmetric 5, 6 or 7 membered heterocyclic group, and the configuration at the carbon atoms which bear R1and R2is such that the compound (2) is the meso-diastereomer which means that the configuration at the carbon atoms which bear R1and R2is (S,R) or (R,S);

[0112] (d) at least one of R3and R4is hydrogen or Cs-Cw-cycloalkyl, such as cyclopentyl or cyclohexyl, where Cs-Cw-cycloalkyl is unsubstituted or substituted as described above.

[0113] Preferred compounds, which are suitable as phosphorus organic ligands (2) are

[0114] i) compounds formula (2), where both R1and R2are hydrogen and both R3and R4are in particular phenyl, such as 1,2-bis(diphenylphosphino)ethane and 1 ,2-bis(diphenylphosphino)propane;

[0115] ii) compounds of the formula (2a-1), where R3and R4are identical or different and selected from hydrogen, cyclohexyl and phenyl

[0116] M / BASFTR-2496-PC

[0117]

[0118] iii) compounds of the formula (2a-2), where R3and R4are identical or different and selected from hydrogen, Ci-Ce alkyl, cyclohexyl and phenyl, provided that one or both of R3and R4are hydrogen or cyclohexyl

[0119]

[0120] iv) compounds of the formula (2b-1), where R3and R4are identical or different and selected from hydrogen, Ci-Ce alkyl, cyclohexyl and phenyl,

[0121]

[0122] v) compounds of the formula (2b-2), where R3and R4are identical or different and selected from hydrogen, cyclohexyl and phenyl, provided that one or both of R3and R4are hydrogen, Ci-Ce alkyl, or cyclohexyl,

[0123]

[0124] vi) compounds of the formula (2c-1), where R3and R4are identical or different and selected from hydrogen, Ci-Ce alkyl, cyclohexyl and phenyl,

[0125] M / BASFTR-2496-PC

[0126]

[0127] vii) compounds of the formula (2c-2), where R3and R4are identical or different and selected from hydrogen, Ci-Ce alkyl, cyclohexyl and phenyl, provided that one or both of R3and R4are hydrogen or cyclohexyl,

[0128]

[0129] viii) compounds of the formula (2d-1), where R3and R4are identical or different and selected from hydrogen, Ci-Ce alkyl, cyclohexyl and phenyl,

[0130]

[0131] (2d-1); and ix) compounds of the formula (2d-2), where R3and R4are identical or different and selected from selected from hydrogen, Ci-Ce alkyl, cyclohexyl and phenyl, provided that one or both of R3and R4are hydrogen or cyclohexyl,

[0132]

[0133] x) compounds of the formula (2e), where R3and R4are identical or different and selected from selected from hydrogen, Ci-Ce alkyl, cyclohexyl and phenyl, including the pure R- and S-enantiomer and the racemic compound (2e),

[0134] M / BASFTR-2496-PC

[0135]

[0136] (2e)

[0137] In a particular group of embodiments of the present invention, the at least one second bidentate phosphorus organic ligand (2) comprises or is a degradation product of the first bidentate phosphorus organic ligand (1) formed during the enantioselective hydrogenation and / or during the workup of the reaction mixture. Such a degradation product is in particular formed by the loss of at least one of the aryl groups of the at least one of the diarylphosphine groups, by racemization or epimerization of the bidentate phosphorus organic ligand (1) and / or by hydrogenation of at least one of the aryl groups of at least one of its diarylphosphine groups. Such degradation products are in particular characterized in that their precursors are ligands (1). In particular they are selected from achiral bidentate ligands having two diarylphosphine groups, chiral bidentate ligands having two diarylphosphine groups and 1 asymmetric carbon atom, achiral bidentate ligands having 1 or 2 monoarylphosphine groups and optionally a diarylphosphine group, chiral bidentate ligands having at least one monoarylphosphine group and optionally a diarylphosphine group, achiral bidentate ligands having 1 or 2 arylcycloalkylphosphine groups and optionally a diarylphosphine group, chiral bidentate ligands having 1 or 2 arylcycloalkylphosphine groups group atoms and optionally a diarylphosphine group and mixtures thereof. It is also apparent that in case of the ligand (2) comprising or being a degradation product, the ligand (2) is often a mixture of at least 2 different ligands (2).

[0138] Such degradation products can be described in particular by the formula (2) as described above, where k = 0, where at least one of R1and R2is different from hydrogen and provided that at least one of the provisos c) and d) are met:

[0139] (c) both R1and R2are different from hydrogen and the compound of formula (2) is achiral, because R1and R2are identical or together with the carbon atoms, to which they are bound may form a symmetric 5, 6 or 7 membered carbocyclic group, a symmetric 6, 7 or 8 membered carbobicyclic group or a symmetric 5, 6 or 7 membered heterocyclic group, and the configuration at the carbon atoms which bear R1and R2is such that the compound (2) is the meso-diastereomer which means that the configuration at the carbon atoms which bear R1and R2is (S,R) or (R,S);

[0140] (d) at least one of R3and R4is hydrogen or Cs-Cw-cycloalkyl, such as cyclopentyl or cyclohexyl, where Cs-Cw-cycloalkyl is unsubstituted or substituted as described above.

[0141] M / BASFTR-2496-PCEspecially, the degradation products of the ligand (1) comprise one or more compounds of the formulae (2a-1), (2a-2), (2b-1), (2b-2), (2c-1), (2c-2), (2d-1) and (2d-2), depending on the bidentate organic ligand (1).

[0142] In particular during the catalytic hydrogenation, and especially after the initial phase, the molar ratio of the second bidentate phosphorus organic ligand (2) to the rhodium atoms is the range of 0.1:1 to 1.0:1, especially 0.1:1 to 0.8:1.

[0143] The process according to the invention relates to the preparation of optically active aldehydes or ketones by asymmetric hydrogenation of prochiral a,p-unsaturated aldehydes or ketones. The process according to the invention is particularly suitable for the preparation of optically active aldehydes by asymmetric hydrogenation of prochiral a,p-unsaturated aldehydes.

[0144] In a preferred embodiment of the use or process according to the invention, the prochiral a,p-unsaturated carbonyl compound is selected from compounds of the formula (V)

[0145] R5O

[0146]

[0147] in which

[0148] R5, R6are different from one another and each is a linear, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more, e.g. 1, 2, 3, 4 or 5, preferably nonconjugated ethylenic double bonds, and which is unsubstituted or carries one or more, e.g. 1, 2, 3 or 4, identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ce- to Cw-aryl and C3- to Cg-hetaryl;

[0149] R7is hydrogen or a linear, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more, e.g. 1, 2, 3, 4 or 5, preferably nonconjugated ethylenic double bonds, and which is unsubstituted or carries one or more, e.g. 1, 2, 3 or 4, identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ce- to Cw-aryl and C3- to Cg-hetaryl;

[0150] or

[0151] R7together with one of the radicals R5or R6, can also be a 3- to 25-membered alkylene group, in which 1 , 2, 3 or 4 nonadjacent CH2 groups can be replaced by O or N-R9c, where the alkylene group is saturated or has one or more, e.g. 1, 2,

[0152] M / BASFTR-2496-PC3, 4 or 5, preferably nonconjugated ethylenic double bonds, and where the alkylene group is unsubstituted or carries one or more, e.g. 1 , 2, 3 or 4, identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ci- to C4-alkyl, Ce- to Cw-aryl and C3- to Cg-hetaryl, where two substituents also together can be a 2- to 10-membered alkylene group, where the 2- to

[0153] 10-membered alkylene group is saturated or has one or more, e.g. 1, 2, 3 or 4, nonconjugated ethylenic double bonds, and where the 2- to 10-membered alkylene group is unsubstituted or carries one or more, e.g. 1 , 2, 3 or 4, identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ce- to Cw-aryl and C3- to Cg-hetaryl;

[0154] where

[0155] R8is hydrogen, Ci- to Ce-alkyl, Ce- to Cw-aryl, C7- to Cw-aralkyl or C7- to C12- alkylaryl;

[0156] R9a, R9bare in each case independently of one another hydrogen, Ci- to Ce-alkyl,

[0157] Ce- to Cw-aryl, C7- to Cw-aralkyl or C7- to Cw-alkylaryl, or

[0158] R9aand R9btogether can also be an alkylene chain having 2 to 5 carbon atoms, which can be interrupted by N or O; and

[0159] R9cis hydrogen, Ci- to Ce-alkyl, Ce- to Cw-aryl, C7- to Cw-aralkyl or C7- to C12- alkylaryl.

[0160] The linear, branched or cyclic hydrocarbon radicals having 1 to 25 carbon atoms specified in the definition of radicals R5, R6and R7are usually linear Ci- to C25-alkyl groups, linear C2- to C25-alkenyl groups, linear C4- to C25-alkadienyl groups, branched C3- to C25-alkyl groups, branched C3- to C25-alkenyl groups, branched C5- to C25-alkadienyl groups, and also C3- to C25-cycloalkyl groups or C3- to C24-cycloalkyl groups which are substituted by one or more, e.g. by 1, 2, 3 or 4, Ci- to C4-alkyl groups, as defined above. The cyclic hydrocarbon radicals both also include cyclic hydrocarbon radicals which have a phenyl ring which optionally carries one or more, e.g. 1, 2, 3, 4, 5 or 6, Ci-C4-alkyl groups, where the phenyl ring is bonded directly to the ethylenically unsaturated double bond or the carbonyl group in formula (V) or is bonded via a Ci-Ce-alkylene group.

[0161] An alkenyl group is understood as meaning a linear or branched aliphatic hydrocarbon radical which is monounsaturated. An alkdienyl group is understood as meaning a linear or branched aliphatic hydrocarbon radical which is diunsaturated. The 3- to 25-membered alkylene groups specified in the definition of the radical R7that are

[0162] M / BASFTR-2496-PCsaturated are generally linear or branched C3- to C25-alkylene groups, as defined above.

[0163] The 3- to 25-membered alkylene groups which have one or more, e.g. 1, 2, 3 or 4, nonconjugated ethylenic double bonds specified in the definition of the radical R7are generally linear or branched C3- to C25-alkenylene groups, as defined above.

[0164] Preferably, one of the radicals R5, R6is methyl or ethyl, in particular methyl, and the other radical is an linear, branched or cyclic hydrocarbon radical having 3 to 25 carbon atoms which is saturated or has one or more. e.g. 1, 2, 3, 4 or 5, preferably nonconjugated ethylenic double bonds, and which is unsubstituted or carries one or more, e.g. 1, 2, 3 or 4, identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ce- to Cw-aryl and C3- to Cg-hetaryl.

[0165] In particular, one of the radicals R5, R6is methyl or ethyl, in particular methyl, and the other radical is an linear, branched or cyclic hydrocarbon radical having 3 to 25 carbon atoms which is saturated or has one or more, e.g. 1, 2 or 3, preferably nonconjugated ethylenic double bonds.

[0166] R7is in particular hydrogen.

[0167] In a very preferred embodiment of the use or process according to the invention, the prochiral a,p-unsaturated carbonyl compound is selected from compounds of the general formula (Va) and (Vb)

[0168]

[0169] in which

[0170] R5, R6is in each case an linear or branched hydrocarbon radical having 2 to 25, in particular having 3 to 20, carbon atoms which is saturated or has 1 , 2, 3, 4 or 5 nonconjugated ethylenic double bonds.

[0171] Accordingly, the use or process according to the invention can be applied, by way of asymmetric hydrogenation of prochiral a,p-unsaturated aldehydes or ketones of the general formulae (V), (Va) or (Vb), to prepare the corresponding a,p-saturated aldehydes or ketones of the formula (VI) in optically active form, where the carbon

[0172] M / BASFTR-2496-PCatom which carries the radicals R5and R6constitutes the asymmetry center generated by the hydrogenation.

[0173]

[0174] In formula (VI), R5, R6and R7have the meanings specified for formula (V), in particular those specified for the formulae (Va) and (Vb). Especially R7is H.

[0175] The asymmetric, i.e. enantioselective hydrogenation according to the invention of the a,p-unsaturated aldehydes of the formulae (Va) or (Vb) renders accessible the corresponding a,p-saturated aldehydes. The compounds of the formulae (Va) and (Vb) constitute E / Z double-bond isomers relative to one another. In principle, the correspondingly optically active aldehydes are accessible starting from both doublebond isomers of the formulae (Va) and (Vb). Depending on the choice of the enantiomeric form of the catalyst of formulae (I), (I. a) or (l.a-1), i.e. depending especially on whether the (+) or (-) enantiomer of the chiral ligand (1) is chosen, preferably one of the enantiomers of the optically active aldehyde is obtained by means of the process of the invention from the E or Z double-bond isomer of formulae (Va) or (Vb) used. The same is true for the aforementioned substrate and product classes. In principle, it is also possible to react mixtures of the two double-bond isomers in a manner according to the invention. This gives mixtures of the two enantiomers of the desired target compound.

[0176] Examples of optically active aldehydes or ketones which can be prepared using the process according to the invention include the following compounds:

[0177]

[0178] (VI-7)

[0179] M / BASFTR-2496-PC

[0180]

[0181] (VI-22) (VI-23)

[0182] The process according to the invention is particularly preferably suitable for the preparation of optically active citronellal of the formula (VI’)

[0183]

[0184] in which * denotes the asymmetry center; by asymmetric hydrogenation of geranial of the formula (Va-1) or of neral of the formula (Vb-1)

[0185]

[0186] Mixtures of geranial and neral can also be reacted in the manner according to the invention, wherein, as described above, mixtures of D- or L-citronellal are obtained which are optically active if the two enantiomers are not present therein in equal parts.

[0187] M / BASFTR-2496-PCOf particular preference in the context of the process according to the invention is the preparation according to the invention of D-citronellal by asymmetric hydrogenation of neral or geranial.

[0188] The preparation process according to the invention is carried out in the presence of the rhodium, a first bidentate chiral phosphorus organic ligand (1) having two coordinating phosphorus atoms in the form of diaryl substituted phosphorus atoms and a second bidentate phosphorus organic ligand (2) having two coordinating phosphorus atoms, where the second bidentate ligand (2) is distinct from the first bidentate chiral ligand, as homogeneous hydrogenation catalyst. The catalyst is hereinafter referred to as rhodium catalyst.

[0189] The active species of the rhodium catalyst is formed by the reaction of a rhodium compound and the first chiral bidentate phosphorus organic ligand (1). The rhodium catalyst may be a mixture of a preformed complex compound comprising rhodium and the first ligand (1) with the second ligand (2). Typically, the rhodium catalyst is formed in situ from a suitable rhodium compound, the first ligand (1) and the second ligand (2). For example, it is possible to form the rhodium catalyst by reacting a suitable rhodium compound and a first ligand (1) followed by the addition of the second ligand (2) to the reaction product of the suitable rhodium compound and the first ligand (1). However, it is also possible to provide the rhodium compound and the first ligand (1) and the second ligand (2) to the reaction in any order. In particular under continuous reaction conditions, it is possible to add the required first ligand (1) and the second ligand (2) and / or the rhodium precursor compounds in any order that is required to maintain the above ratios of rhodium atoms, ligand (1) and ligand (2) in the reaction system.

[0190] Suitable rhodium compounds are in particular those which are soluble in the selected reaction medium, such as, for example, rhodium (0), rhodium(l), rhodium(ll) and rhodium(lll) salts such as e.g. rhodium(lll) chloride, rhodium(lll) bromide, rhodium(lll) nitrate, rhodium(lll) sulfate, rhodium(ll) or rhodium(lll) oxide, rhodium(ll) or rhodium(lll) acetate, rhodium(ll) or rhodium(lll) carboxylate, Rh(acac)3, [Rh(cod)CI]2, [Rh(cod)2] BF4, Rh2(OAc)4, bis(ethylene)rhodium(l)acac, Rh(CO)2acac, [Rh(cod)OH]2, [Rh(cod)OMe]2, Rh4(CO)i2 or Rhe(CO)i6, where "acac" is an acetylacetonate ligand, "cod" is a cyclooctadiene ligand and "OAc" is an acetate ligand.

[0191] Preferably, the rhodium compound used is Rh(OAc)a, [Rh(cod)CI]2, Rh(CO)2 acetylacetonate, [Rh(cod)OH]2, [Rh(cod)OMe]2, Rh4(CO)i2 or Rhe(CO)i6, Rh2(OAc)4 and bis(ethylene)rhodium(l) acetylacetonate. In particular, the rhodium compound used is Rh(CO)2acac, Rh2(OAc)4 and bis(ethylene)rhodium(l) acetylacetonate.

[0192] M / BASFTR-2496-PCThe specified and further suitable rhodium compounds or rhodium complexes are known and adequately described in the literature or can be prepared by the person skilled in the art analogously to the compounds already known.

[0193] The amount of rhodium in the asymmetric hydrogenation of a,p-unsaturated aldehydes and ketones in a batch procedure is usually in the range of about 0.001 to about 1 mol%, preferably in the range of about 0.002 to about 0.5 mol%, in particular in the range of about 0.005 to about 0.2 mol%, based on the rhodium atoms present in relation to the amount of substrate to be hydrogenated. In continuous procedures the amount of rhodium in the asymmetric hydrogenation of a,p-unsaturated aldehydes and ketones typically is typically in the range of 100 to 10,000 ppm, in particular in the range of 200 to 5,000 ppm, based on the reaction mixture. Here, the amounts in ppm are based on the relative weight of rhodium in the reaction mixture.

[0194] In a preferred embodiment of the process according to the invention, the rhodium catalyst comprising rhodium and the first ligand (1) and optionally the second ligand (2) is pretreated before the hydrogenation with a gas mixture comprising carbon monoxide and hydrogen, and / or the asymmetric hydrogenation is carried out in the presence of carbon monoxide additionally introduced to the reaction mixture.

[0195] This means that the rhodium catalyst comprising rhodium and the first ligand (1) and optionally the second ligand (2) is either pretreated before the asymmetric hydrogenation with a gas mixture which comprises carbon monoxide and hydrogen (i.e. a so-called preformation is carried out) or the asymmetric hydrogenation is carried out in the presence of carbon monoxide additionally introduced into the reaction mixture or a preformation is carried out and then the asymmetric hydrogenation is carried out in the presence of carbon monoxide additionally introduced to the reaction mixture.

[0196] Preferably, in this preferred embodiment, the rhodium catalyst comprising rhodium and the first ligand (1) and optionally the second ligand (2) is pretreated with a gas mixture comprising carbon monoxide and hydrogen and the asymmetric hydrogenation is carried out in the presence of carbon monoxide additionally introduced to the reaction mixture.

[0197] In this preferred embodiment, the specified pretreatment is carried out with a gas mixture comprising 20 to 90% by volume carbon monoxide, 10 to 80% by volume hydrogen and 0 to 5% by volume further gases, where the specified volume fractions add up to 100% by volume, at a pressure of 5 to 100 bar. Additionally, excess carbon monoxide is separated off from the resulting catalyst prior to use in the asymmetric hydrogenation.

[0198] M / BASFTR-2496-PCThe term excess carbon monoxide is to be understood here as meaning the carbon monoxide which is present in the resulting reaction mixture in gaseous or dissolved form and is not bonded to the final rhodium catalyst or its precursor catalyst.

[0199] Accordingly, the excess carbon monoxide not bonded to the catalyst is removed at least largely, i.e. to an extent that any residual amounts of dissolved carbon monoxide do not make themselves noticeably disruptive in the subsequent hydrogenation. This is usually ensured if about 90%, preferably about 95% or more of the carbon monoxide used for the preformation are separated off. Preferably, the excess carbon monoxide is removed completely from the catalyst obtained by preformation.

[0200] The separation of the excess carbon monoxide from the resulting catalyst or from the reaction mixture comprising the catalyst can take place in different ways. Preferably, the rhodium catalyst or the mixture comprising the catalyst obtained by preformation is decompressed to a pressure of up to about 5 bar (absolute), preferably, specifically when carrying out the preformation in the pressure range from 5 to 10 bar, to a pressure of less than 5 bar (absolute), preferably to a pressure in the range from about 1 bar to about 5 bar, preferably 1 to less than 5 bar, particularly preferably to a pressure in the range from 1 to 3 bar, very particularly preferably to a pressure in the range from about 1 to about 2 bar, particularly preferably to atmospheric pressure, meaning that gaseous, nonbound carbon monoxide escapes from the product of the preformation.

[0201] The aforementioned decompression of the preformed catalyst can take place for example using a high-pressure separator, as is known per se to the person skilled in the art. Separators of this type in which the liquid is in the continuous phase are described for example in: Perry’s Chemical Engineers’ Handbook, 1997, 7th edition, McGraw-Hill, p. 14.95 and 14.96; the prevention of a possible drop entrainment is described on pages 14.87 to 14.90. The decompression of the preformed catalyst can take place in one stage or two stages until the desired pressure in the range from 1 bar to about 5 bar is reached, during which the temperature usually drops to 10 to 40°C.

[0202] Alternatively, the separation off of excess carbon monoxide can be achieved by so-called stripping of the catalyst or of the mixture comprising the catalyst with a gas, advantageously with a gas that is inert under the reaction conditions. Here, the term stripping is understood by the person skilled in the art as meaning the introduction of a gas into the catalyst or the reaction mixture comprising the catalyst, as described for example in W. R. A. Vauck, H. A. Muller, Grundoperationen chemischer Verfahrenstechnik [Basic operations of chemical processing technology], Deutscher Verlag fur Grundstoffchemie Leipzig, Stuttgart, 10th edition, 1984, page 800. Suitable inert gases which may be mentioned here by way of example are: hydrogen, helium, neon, argon, xenon, nitrogen and / or CO2, preferably hydrogen, nitrogen, argon.

[0203] M / BASFTR-2496-PCPreferably, the asymmetric hydrogenation is then carried out with hydrogen which has a carbon monoxide content in the range from 50 to 3000 ppm, in particular in the range from 100 to 2000 ppm, specifically in the range from 200 to 1000 ppm and very specifically in the range from 400 to 800 ppm.

[0204] If a preforming of the catalyst is carried out, usually the rhodium catalyst (I), (I. a) or (l.a-1) and if desired the substrate to be hydrogenated asymmetrically are dissolved in a suitable solvent or solution medium that is inert under the reaction conditions, such as, for example, ether, tetrahydrofuran, methyltetrahydrofuran, aromatic hydrocarbons and aromatic chlorohydrocarbons, such as toluene, xylene, chlorobenzene, benzene and biphenyl ether, octadecanol, texanol, Marlotherm, Oxo Oil 9N (hydroformylation products from isomeric octenes, BASF SE), citronellal, citronellol, linalool, 3,7-dimethyl-1-octanol (106-21-8) ,1-octanol (and its constitutional isomers, i.e 2-octanol, 3-octanol), menthol (and its diastereoisomers), isopulegol (and its diastereoisomers), 1 -decanol (and its constitutional isomers), 1-dodecanol (and its constitutional isomers), 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2H-tetrahydropyran-4-carboxylic acid methyl ester (110238-91-0), ethyl acetate, hexyl hexanoate (6378-65-0), decyl decanoate (1654-86-0), hexyl octanoate (1117-55-1), trans-3,7-dimethyl-2,6-octadienyl 5,9,13-trimethyl-4,8,12-tetradecatrienoate (51-77-4) (and its E / Z isomers); (E,Z)-2,13-octadecadien-1-ol acetate (86252-74-6) (and its E / Z isomers), geranyl hexanoate (10032-02-7), 3,7-dimethyl-6-octen-1-yl 3,7-dimethyl-6-octenoate (82766-40-3) (and its diastereoisomers), 3,7-dimethyl-6-octen-1-yl octanoate (72934-05-5), 3,7-dimethyl-6-octenoic acid (502-47-6), 3,7-dimethyloctanoic acid (5698-27-1), 3,7-dimethyl-2,6-octadien-1-yl-3,7-dimethyl-2,6-octadienoate (1639348-45-0) (and its E / Z isomers), 3,7-dimethyl-2,6-octadien-1-yl 5,9,13-trimethyl-4,8,12-tetradecatrienoate (16898-88-7), ethyl 5,9, 13, 17-tetramethyl-4,8, 12, 16-octadecatetraenoate (63839-64-5), phenylcyclohexan, tetralin, dichloromethane, pentadecalactone (106-02-5), dodecalactone (947-05- 7)and the like as well as mixtures of the aforementioned organic solvents. The substrate to be reacted, the product or any high-boiling byproducts produced during the reaction can also serve as solution medium. A gas mixture which comprises hydrogen and carbon monoxide is injected into the resulting solution, advantageously in a suitable pressurized reactor or autoclave, at a pressure of usually about 5 to about 350 bar, preferably from about 20 to about 200 bar and particularly preferably from about 50 to about 100 bar. Preferably, for the preformation a gas mixture is used which comprises about

[0205] 30 to 99% by volume hydrogen,

[0206] 1 to 70% by volume carbon monoxide and

[0207] 0 to 5% by volume further gases,

[0208] M / BASFTR-2496-PCwhere the data in % by volume must add up to 100% by volume.

[0209] For the preformation, particular preference is given to using a gas mixture which comprises about

[0210] 40 to 80% by volume hydrogen,

[0211] 20 to 60% by volume carbon monoxide and

[0212] 0 to 5% by volume further gases,

[0213] where the data in % by volume must add up to 100% by volume.

[0214] A gas mixture particularly preferred for the preformation is so-called synthesis gas, which usually consists of about 35 to 55% by volume of carbon monoxide alongside hydrogen and traces of further gases.

[0215] The preformation of the catalyst is usually carried out at temperatures of from about 25°C to about 100°C, preferably at about 40°C to about 80°C. If the preformation is carried out in the presence of the substrate to be hydrogenated asymmetrically, the temperature is advantageously selected such that it does not result, to a troublesome extent, in an isomerization of the double bond to be hydrogenated. The preformation is usually terminated after about 1 h to about 24 h, often after about 1 to about 12 h.

[0216] Following the optional preformation to be carried out, the asymmetric hydrogenation of the selected substrate is carried out in accordance with the invention. Following a preceding preformation, the hydrogenation of selected substrate can generally be successfully carried out with or without the introduction of additional carbon monoxide. If no preformation is carried out, the asymmetric hydrogenation according to the invention can be carried out either in the presence of carbon monoxide introduced into the reaction system or without the introduction of carbon monoxide. Advantageously, a preformation is carried out as described and additional carbon monoxide is added to the reaction mixture during the asymmetric hydrogenation.

[0217] If carbon monoxide is introduced into the reaction system, the introduction can be carried out in various ways: thus, for example, the carbon monoxide can be admixed with the hydrogen used for the asymmetric hydrogenation, or else be metered in directly in gaseous form into the reaction solution. A further option consists for example in adding compounds to the reaction mixture which readily release carbon monoxide, such as for example formates or oxalyl compounds.

[0218] The carbon monoxide is preferably admixed with the hydrogen used for the asymmetric hydrogenation.

[0219] M / BASFTR-2496-PCThe asymmetric hydrogenation according to the invention is advantageously carried out at a pressure of about 5 to about 200 bar, in particular about 10 to about 100 bar, specifically at about 60 to about 100 bar and a temperature of generally about 0°C to about 100°C, preferably about 0°C to about 30°C, in particular at about 10°C to about 30°C.

[0220] The selection of the solvent to be used for carrying out the asymmetric hydrogenation according to the invention is less important. In any case, advantages according to the invention also arise in different solvents. Suitable solvents are, for example, those mentioned for carrying out the preformation according to the invention. With particular advantage, the asymmetric hydrogenation is carried out in the same solvent as the preformation optionally carried out beforehand.

[0221] Suitable solvents include ethers, such as tetrahydrofuran, dioxane, methyltetrahydrofuran, aromatic hydrocarbons and aromatic chlorohydrocarbons, such as toluene, xylene, chlorobenzene, benzene, biphenyl ether, octadecanol, texanol, Marlotherm, Oxo Oil 9N (hydroformylation products from isomeric octenes, BASF SE), citronellal, citronellol, linalool, 3, 7-dimethyl-1 -octanol (106-21-8) ,1-octanol (and its constitutional isomers, i.e 2-octanol, 3-octanol), menthol (and its diastereoisomers), isopulegol (and its diastereoisomers), 1-decanol (and its constitutional isomers), 1-dodecanol (and its constitutional isomers), 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2H-tetrahydropyran-4-carboxylic acid methyl ester (110238-91-0), ethyl acetate, hexyl hexanoate (6378-65-0), decyl decanoate (1654-86-0), hexyl octanoate (1117-55-1), trans-3,7-dimethyl-2,6-octadienyl 5,9, 13-trimethyl-4, 8,12-tetradecatrienoate (51-77-4) (and its E / Z isomers), (E,Z)-2,13-octadecadien-1-ol acetate (86252-74-6) (and its E / Z isomers), geranyl hexanoate (10032-02-7), 3,7-dimethyl-6-octen-1-yl 3,7-dimethyl-6-octenoate (82766-40-3) (and its diastereoisomers), 3,7-dimethyl-6-octen-1-yl octanoate (72934-05-5), 3,7-dimethyl-6-octenoic acid (502-47-6), 3,7-dimethyloctanoic acid (5698-27-1), 3,7-dimethyl-2,6-octadien-1-yl-3,7-dimethyl-2,6-octadienoate (1639348-45-0) (and its E / Z isomers), 3,7-dimethyl-2,6-octadien-1-yl 5,9,13-trimethyl-4,8,12-tetradecatrienoate (16898-88-7), ethyl 5,9, 13, 17-tetramethyl-4,8, 12, 16-octadecatetraenoate (63839-64-5), phenylcyclohexan, tetralin, dichloromethane, pentadecalactone (106-02-5), dodecalactone (947-05-7) and the like as well as mixtures of the aforementioned organic solvents. Solvents such as citronellal or other organic solvents such as texanol (2,2,4-trimethyl-1,3-pentanediol monoisobutyrate) are particularly suitable.

[0222] Suitable reaction vessels for carrying out the asymmetric hydrogenation according to the invention are in principle all those which permit reactions under the specified

[0223] M / BASFTR-2496-PCconditions, in particular pressure and temperature, and are suitable for hydrogenation reactions, such as, for example, autoclaves, tubular reactors, bubble columns, etc.

[0224] If the hydrogenation of the process according to the invention is carried out using high-boiling, generally viscous solvents, as are described for example above in connection with the use in the course of the pretreatment of the catalyst (for example the specified solvents octadecanol, biphenyl ether, texanol (2,2,4-trimethyl-1,3-pentanediol monoisobutyrate), Marlotherm®, Oxo Oil 9N) or if the hydrogenation is carried out without the additional use of solvents, but with accumulation of the high-boiling components arising as by-products to a low degree (such as, for example, dimers or trimers which are formed by reactions of the starting materials and / or the products and subsequent secondary reactions), it may be advantageous to provide good gas introduction and thorough mixing of gas phase and condensed phase. This is achieved for example by carrying out the hydrogenation step of the process according to the invention in a gas circulation reactor. Gas circulation reactors are known per se to the person skilled in the art and are described for example in P. Trambouze, J.-P. Euzen, Chemical Reactors, Ed. Technip, 2004, p. 280-283 and P. Zehner, R. Benfer, Chem. Eng. Sci. 1996, 51, 1735-1744, and also e.g. in EP 1 140349. In principle, it is also possible to carry out the reaction in the product as solvent, for example in citronellal when the starting material is neral or geranial.

[0225] When using a gas circulation reactor as specified above, it has proven to be particularly advantageous to introduce the gas or gas mixture (hydrogen comprising carbon monoxide) to be used in parallel to the starting materials to be introduced into the reactor and / or the circulating reaction mixture or the catalyst by means of a single nozzle or a two-material nozzle into the gas circulation reactor. Here, the two-material nozzle is notable for the fact that liquid and gas to be introduced into the reactor arrive through two separate concentric tubes under pressure to the mouth of the nozzle, where they are combined with one another.

[0226] The process according to the invention can be successfully carried out with and without the addition of tertiary amines. Preferably, the process according to the invention is carried out in the absence, i.e. without the addition of additional tertiary amines, or in the presence of only catalytic amounts of additional tertiary amines. The amount of amine used here can be between 0.5 and 500 mol equivalents, based on the amount of rhodium present in the catalyst used, and preferably is 1 to 100 mol equivalents based on the amount of the rhodium. The choice of tertiary amine is not critical. As well as short-chain alkylamines, such as, for example, triethylamine, it is also possible to use long-chain alkylamines, such as for example tridodecylamine or bisdecylamine. In the context of a preferred embodiment, the hydrogenation process according to the invention is carried out in the presence of a tertiary amine, preferably tridodecylamine,

[0227] M / BASFTR-2496-PCin an amount of about 2 to 30 mol equivalents, preferably about 5 to 20 mol equivalents and particularly preferably 5 to 15 mol equivalents, based on the amount of rhodium present in the catalyst used.

[0228] The process according to the invention can also be successfully carried out with and without the addition of tertiary phosphines. Suitable tertiary phosphines include trialkyl phosphines, cycloalkyldialkyl phosphines, aryldialkyl phosphines, alkyldiaryl phosphines, cycloalkyldiaryl phosphines and triarylphosphines. Here, the radicals alkyl, cycloalkyl and aryl are as defined above. Alkyl may also have a phosphinoxide group, such as diarylphosphine oxide, alkylarylphosphine oxide or cycloalkylaryl phosphinoxide.

[0229] Suitable tertiary phosphines are those disclosed in WO 2016 / 097242 as compounds of the formula (I). Examples of such compounds include, but are not limited to

[0230] (2-(diphenylphosphoryl)-1-methylpropyl))diphenylphosphane, including its (R,R)-enantiomer (= (R,R)-chiraphos monoxide) and its (S,S)-enantiomer (= (S,S)-chiraphos monoxide), and its racemate,

[0231] triphenylphosphine,

[0232] cyclopentyldiphenylphosphine,

[0233] 2-butyldiphenylphosphine,

[0234] cyclohexyldiphenylphosphine,

[0235] isopropyldiphenylphosphine,

[0236] [5-(diphenylphosphanylmethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyldiphenyl- phosphane monoxide, including its (4S,5S) and (4R,5R) enantiomers and its racemate,

[0237] [5-(1-diphenylphosphanylethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyldiphenyl- phosphane monoxide, including its (4S,5S) and (4R,5R) enantiomers and its racemate,

[0238] [2-diphenylphosphanylcyclohexyl]diphenylphosphane monoxide, including its (1S,2S) and (1R,2R) enantiomers and its racemate,

[0239] [4-diphenylphosphanyltetrahydrofuran-3-yl]diphenylphosphane monoxide, including its (3S,4S) and (3R,4R) enantiomers and its racemate,

[0240] [2-diphenylphosphanyl-3-bicyclo[2.2.1 ]hept-5-enyl]diphenylphosphane monoxide, including its (1S,2R,3R,4R), (1R,2S,3R,4R), (1S,2R,3S,4S), (1R,2S,3S,4S) isomers, and enantiomer and diastereomer mixtures thereof,

[0241] [1-benzyl-4-diphenylphosphanylpyrrolidin-3-yl]diphenylphosphane monoxide, including its (3S,4S) and (3R,4R) enantiomers and its racemate,

[0242] [3-diphenylphosphanyl-1-methylbutyl]diphenylphosphane monoxide, including its (1S,3S) and (1R,3R) enantiomers and its racemate,

[0243] M / BASFTR-2496-PCand mixtures thereof.

[0244] The tertiary phosphines are typically used in amounts of 0.01 to 0.2 mol per 1 mol of rhodium in the reaction mixture.

[0245] The reaction is advantageously terminated when the target compound is present in the desired yield and the desired optical activity, i.e. with the desired enantiomer excess (ee) in the reaction mixture, as can be established by the person skilled in the art by means of routine experiments for example by means of chromatographic methods. Usually, the hydrogenation is terminated after about 1 to about 150 h, often after about 2 to about 24 h.

[0246] By means of the use or process according to the invention it is possible to provide optically active carbonyl compounds, in particular optically active aldehydes, in high yields and enantiomer excesses. Usually, the desired asymmetrically hydrogenated compounds are obtained in an enantiomer excess of at least 80% ee, often with an enantiomer excess with about 85 to about 99% ee. In this connection, it is to be noted that the maximum achievable enantiomer excess may depend on the purity of the substrate used, in particular with regard to the isomer purity of the double bond to be hydrogenated.

[0247] Consequently, suitable starting substances are in particular those which have an E / Z isomer ratio of at least about 90:10, preferably at least about 95:5 with regard to the E / Z double-bond isomers. Likewise suitable starting substances are those which have an E / Z isomer ratio of at most about 10:90, preferably at most about 5:95 with regard to the E / Z double-bond isomers.

[0248] By means of the preforming and / or by means of the carbon monoxide additionally introduced into the reaction system, the homogeneous catalyst of formulae (I), (I. a) or (La-1) used can be stabilized, as a result of which, on the one hand, the service life of the catalysts is considerably increased and, on the other hand, the reusability of the catalyst is facilitated.

[0249] Thus, for example, the resulting reaction product can be removed from the reaction mixture by processes known per se to the person skilled in the art, such as e.g. by distillation, and the catalyst that is left behind can be used in the course of further reactions, optionally after repeated preformation.

[0250] The process according to the invention can accordingly be operated either discontinuously or semicontinuously as well as continuously and is suitable in particular for reactions on an industrial scale.

[0251] M / BASFTR-2496-PCIn a particularly preferred embodiment of the use or process according to the invention, neral or geranial, which comprises up to about 5 mol%, preferably up to about 2 mol%, of the respective double-bond isomers, is converted to optically active citronellal.

[0252] According to this preferred embodiment it is also preferred to use a rhodium catalyst, which comprises an optically active bidentate ligand (1) having an enantiomeric excess of at least 90% ee, in particular at least 95% ee. In this context it is further preferred to use a ligand (1) that is selected from the compounds of the formulae (1a) to (1d) and the enantiomers thereof, and in particular is the compound of formula (1a) or its enantiomer, i.e. (R,R)-chiraphos or (S,S)-chiraphos.

[0253] In a particularly preferred embodiment of the use or process according to the invention, neral which comprises up to about 5 mol%, preferably up to about 2 mol% of geranial is hydrogenated in the presence of a rhodium catalyst, where the first ligand (1) is (R,R)-chiraphos, to yield D-citronellal, where the (R,R)-chiraphos has an enantiomeric excess of at least 90% ee, in particular at least 95% ee. In another particularly preferred embodiment of the use or process according to the invention, neral which comprises up to about 5 mol%, preferably up to about 2 mol% of geranial is hydrogenated in the presence of a rhodium catalyst, where the first ligand (1) is (S,S)-chiraphos, to yield L-citronellal, where the (S,S)-chiraphos has an enantiomeric excess of at least 90% ee, in particular at least 95% ee. In these particularly preferred embodiments it is also preferred that the rhodium-catalyst is preformed under the conditions mentioned above and then the asymmetric hydrogenation is carried out in the presence of hydrogen which comprises in particular 50 to 3000 ppm of carbon monoxide.

[0254] A further aspect of the present invention relates to a process for the preparation of optically active menthol using optically active citronellal prepared by the process according to the invention. The preparation of optically active menthol proceeding from optically active citronellal is known. A key step here is the cyclization of optically active citronellal to optically active isopulegol, as described for example in EP 1 225 163 A2.

[0255] The process for the preparation of optically active menthol comprises the following steps:

[0256] • preparation of optically active citronellal by asymmetric hydrogenation of geranial of the formula (Va-1) or of neral of the formula (Vb-1) by the process according to the invention,

[0257] • cyclization of the optically active citronellal prepared in this way to give optically active isopulegol in the presence of a Lewis acid, and

[0258] • hydrogenation of the optically active isopulegol prepared in this way to give optically active menthol.

[0259] M / BASFTR-2496-PCAs shown below in diagrammatic form for the preparation of L-menthol of the formula (IX), optically active citronellal (VI’) prepared according to the invention can be cyclized in the presence of a suitable acid, in particular a Lewis acid to give L-isopulegol of the formula (VIII) and then hydrogenated to L-menthol.

[0260]

[0261] (VI') (VIII) (IX)

[0262] A further aspect of the present invention accordingly relates to the use of optically active citronellal prepared by the process according to the invention for preparing optically active menthol. In particular, the invention relates to the use of the D-citronellal prepared by the process according to the invention for preparing optically active L-menthol.

[0263] As indicated above, the catalyst composition has special characteristics. It was surprisingly found to be particularly beneficial for catalyzing a reaction such as hydrogenation of an a,p-unsaturated olefinic double bond, which may optionally enantioselective, of an optionally prochiral a,p-unsaturated carbonyl compound.

[0264] The examples below serve to illustrate the invention without adversely affecting it in any way:

[0265] EXAMPLES

[0266] Abbreviations:

[0267] acac: acetylacetonate

[0268] (R,R)-chiraphos: (2R,3R)-bis(diphenylphosphino)butane (CAS: 74839-84-2) dppe: 1,2-Bis(diphenylphosphino)ethane (CAS: 1663-45-2)

[0269] LRh: molar ratio of ligands (i.e. the total amount of ligands (1)+(2)) to rhodium P:Rh: molar ratio of phosphorus atoms to rhodium atoms

[0270] Texanol™: 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate

[0271] v / v: volume to volume

[0272] mol eq.: molar equivalent

[0273] %ee: percent enantiomeric excess

[0274] M / BASFTR-2496-PCI Continuously operated enantioselective catalytic hydrogenation of neral to prepare citronellal

[0275]

[0276] 1 to the i with a chiral obtained

[0277]

[0278] with where the molar excess of

[0279]

[0280]

[0281] is increased from 1.4 to 1.8.2 the reaction

[0282] In a continuously operated apparatus, a solution of Rh(CO)2acac and (R.R)-chiraphos in a molar ratio of L:Rh=1.4:1 in Citronellal was exposed to mixture of CO and H2 (1:1 v / v) at a pressure of 80 bar at 60°C in a catalyst preformation reactor. This solution is then filled in the first hydrogenation reactor unit of a cascade of two sequential hydrogenation reactors, and the same volume of neral (neral / geranial = 98.3:0.4) is added to the first hydrogenation reactor unit. The hydrogenation reactor cascade is fed with 80 bar H2 containing 1000 ppm CO and held at a temperature of 10-25 °C. A feed of neral in the range of 500 kg / h to 1500 kg / h is pumped into the hydrogenation reactors, whereas the catalyst solution is added with the same flow rate, resulting in a constant Rh concentration of about 420 ppm Rh. The product mixture of citronellal and citronellol having a content of > 95 vol% of citronellal (GC) is distilled off at a rate chosen to keep the liquid levels in the unit constant, pumping back the catalyst containing liquid stream from the distillation sump into the preformation reactor. Over a runtime of 130 days, the molar ratio of L to Rh is gradually increased to 1.82:1 (corresponding to a P:Rh ratio of 3.64:1) by addition of (R,R)-chiraphos to compensate partial degradation of (R,R)-chiraphos. The molar ratio of the overall added amounts of (R,R)-chiraphos to Rh(CO)2acac after 130 days was 1.82:1.

[0283] In a specific run a 72% conversion of neral in the first hydrogenation reactor (at >99% conversion in the second reactor) was achieved after a runtime of 130 days at 80 bar of hydrogen, a reaction temperature of 16°C and a Rh concentration of 410 to 430 ppm using a neral feed of 1450 kg / h. In probes taken from the reaction mixture, degradation products resulting from the partial degradation of (R,R)-chiraphos could be identified as bidentate ligands having two P-atoms which are still capable of coordinating the rhodium atoms.

[0284]

[0285] with a chiral obtained

[0286]

[0287] with 1.4 mol eq. of

[0288] In a continuously operated apparatus, a solution of Rh(CO)2acac and (R,R)-chiraphos in a molar ratio of L:Rh=1.4:1 in Citronellal was exposed to mixture of CO and H2 (1:1 v / v) at a pressure of 80 bar at 60°C in a catalyst preformation reactor. This solution is then filled in the first hydrogenation reactor unit and the same volume of neral (neral / geranial = 98.3:0.4) is added. The hydrogenation reactor cascade (two

[0289] M / BASFTR-2496-PCsequential hydrogenation reactors) is fed with 80 bar H2 containing 1000 ppm CO and held at a temperature of 10-25 °C. A feed of neral in the range of 500 kg / h to 1500 kg / h is pumped into the hydrogenation reactors resulting in a constant Rh concentration of 420 ppm Rh. The product mixture is distilled off at a rate chosen to keep the liquid levels in the unit constant, pumping back the catalyst containing liquid stream from the distillation sump into the preformation reactor. Over a runtime of 130 days, the L / Rh ratio was kept at 1.4:1 to 1.5:1 (corresponding to a P:Rh ratio of 2.8:1 to 3.0:1) and the Rh concentration was raised to 490 ppm by addition of (R, R)-chiraphos and Rh(CO)2acac. The molar ratio of the overall added amounts of (R.R)-chiraphos to Rh(CO)2acac after 130 days was 1.50:1.

[0290] In a specific run a 65% conversion of neral in the first hydrogenation reactor (at >99% conversion in the second reactor) was achieved after a runtime of 130 days at 80 bar of hydrogen, a reaction temperature of 18.5 °C and a Rh concentration of 490 ppm using a neral feed of 1450 kg / h.

[0291] II Enantioselective catalytic hydrogenation of neral to prepare citronellal in batch

[0292] Example 3: Hydrogenation with a chiral catalyst obtained by mixing Rh(CO)2acac with 1.7 mol eg. of (R,R)-chiraphos and 0.2 mol eg. of dppe

[0293] :Rh = 3.8:1)

[0294] Rh(CO)2acac (60 mg, 0.23 mmol), (F?,F?)-chiraphos (170 mg, 0.40 mmol) and dppe (20 mg, 0.05 mmol) were dissolved in the texanol (21 ml_, 2,2,4-trimethyl-1,3-pen-tanediol monoisobutyrate, ABCR) and stirred in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gas-dispersion stirrer, 1000 revolutions / min) at 80 bar synthesis gas (H2 / CO = 1:1, vol. / vol.) and 70°C for 16 h. The system is then cooled to 25°C and nitrogen is passed through the solution for two hours (8 l / h). After flushing with nitrogen, neral (20 g, ratio of the double-bond isomers neral / geranial = 98.3:0.4) was added to the autoclave via a lock. The reaction pressure was adjusted to 80 bar by injecting hydrogen gas which comprised 1000 ppm of carbon monoxide. Time / conversion was determined by gas chromatography. After a reaction time of 6 hours, a conversion of 42% was achieved and a yield of 42% of citronellal. After 20 h, the conversion of citral was 98% and the yield of D-citronellal was 98%, with the optical purity being determined as 72.5 %ee.

[0295] An overview of the reaction conditions is given in Table 1 below.

[0296] Conversion rates of neral over time, as measured by GC, and the finally obtained enantiomeric excess %ee are given in Table 2 below.

[0297] M / BASFTR-2496-PCExample 4 (Comparative): Hydrogenation with a chiral catalyst obtained by mixing (Rh(CO)2acac with 1.9 mol eg. of (R,R)-chiraphos in Texanol ( P : R h = 3.8 : 1 )

[0298] An overview of the reaction conditions is given in Table 1 below. The example is carried out as example 3 with the changes stated in Table 1. Conversion rates of neral over time, as measured by GC, and the finally obtained enantiomeric excess %ee are given in Table 2 below.

[0299] Example 5: Hydrogenation with a chiral catalyst obtained by mixing RhfCOhacac with 1.5 mol eg. of (R,R)-chiraphos and 0.4 mol eg. of dppe in citronellal ( P : R h = 3.8 : 1 )

[0300] An overview of the reaction conditions is given in Table 1 below. The example is carried out as example 3 with the changes stated in Table 1.

[0301] Conversion rates of neral over time, as measured by GC, and the finally obtained enantiomeric excess %ee are given in Table 2 below.

[0302] Example 6 (Comparative): Hydrogenation with a chiral catalyst obtained by mixing (Rh(CO)2acac with 1.9 mol eg. of (R,R)-chiraphos in citronellal (P:Rh = 3.8:1)

[0303] An overview of the reaction conditions is given in Table 1 below. The example is carried out as example 3 with the changes stated in Table 1.

[0304] Conversion rates of neral over time, as measured by GC, and the finally obtained enantiomeric excess %ee are given in Table 2 below.

[0305] Table 1: Basic reaction conditions of (Comparative) Examples 4 to 7

[0306] Example Ex. 3 Comp. Ex. 4 Ex. 5 Comp. Ex. 6 Solvent used Texanol Texanol D-Citronellal* D-Citronellal* Concentration of Rh

[0307] in reaction mixture 600 600 600 600 [PPm]

[0308] Concentration of P in

[0309] 700 700 700 700 reaction mixture [ppm]

[0310] Molar ratio of

[0311] 1 : 1.7 : 0.2 1 : 1.9 : 0.0 1 : 1.5 : 0.4 1 : 1.9 : 0 Rh / chiraphos / dppe

[0312]

[0313] *from a previous run having with 88 %ee

[0314] Table 2: Results of the hydrogenations of (Comparative) Examples 4 to 7

[0315] M / BASFTR-2496-PCEx. 3 Comp. Ex. 5 Comp.

[0316] Ex. 4 Ex. 6

[0317] Time [h]

[0318] 0.0017 0 0 0 0 1 5 1 14 7 2 10 2 22 14 Conversion 3 16 4 32 21 rates [%] 4 24 5 45 28

[0319] 5 33 7 57 36 6 42 8 68 44 20 99 30 100 100 %ee 73 81 77 89

[0320]

[0321] M / BASFTR-2496-PC

Claims

Claims1. A process for an enantioselective catalytic hydrogenation of an a,p-unsaturated olefinic double bond of a prochiral a,p-unsaturated carbonyl compound, which comprises subjecting the prochiral a,p-unsaturated carbonyl compound to hydrogen in the presence of a chiral catalyst composition, which comprises rhodium, a first bidentate chiral phosphorus organic ligand (1) having two coordinating phosphorus atoms in the form of diarylphosphine groups and at least one second bidentate phosphorus organic ligand (2) having two coordinating phosphorus atoms, where the second bidentate ligand (2) is distinct from the first bidentate chiral ligand, where during the catalytic hydrogenation the molar ratio of the total amount of the ligands (1) and (2) to the rhodium is at least 1.8: 1 , e. g. in the range of 1.8: 1 to 2.5: 1 , where at least in the initial phase of the enantioselective catalytic hydrogenation the molar ratio of the ligand (1) to rhodium is in the range of 1.0:1 to 1.7:1.

2. The process of claim 1 , where enantioselective catalytic hydrogenation is a continuously operated enantioselective catalytic hydrogenation.

3. The process of any one of the preceding claims, where the molar ratio of the ligand (1) to the rhodium is maintained in the range of 1.0:1 to 1.7:1 by dosing the ligand (1) or (2) into the reaction mixture, such that the molar ratio of the total amount of the ligands (1) and (2) to the rhodium is at least 1.8:1.

4. The process of any one of the preceding claims, where the second bidentate phosphorus organic ligand (2) is distinct from the bidentate phosphorus organic ligand (1) by its substitution pattern on the phosphorus atoms, having a smaller number of asymmetric carbon atoms than ligand (1) or by being an achiral bidentate phosphorus organic ligand.

5. The process of any one of the preceding claims, where the second bidentate phosphorus organic ligand (2) comprises a degradation product of the first bidentate phosphorus organic ligand (1), in particular a degradation product formed by the loss of at least one of the aryl groups of the at least one of the diarylphosphine groups, by racemization or epimerization of the bidentate phosphorus organic ligand (1) and / or by hydrogenation of at least one of the aryl groups of the at least one of its diarylphosphine groups.

6. The process of any one of the preceding claims, where the second bidentate phosphorus organic ligand (2) is selected from achiral bidentate ligands having two diarylphosphine groups, chiral bidentate ligands having two diarylphosphineM / BASFTR-2496-PCgroups and 1 asymmetric carbon atom, achiral bidentate ligands having 1 or 2 monoarylphosphine groups and optionally a diarylphosphine group, chiral bidentate ligands having at least one monoarylphosphine group and optionally a diarylphosphine group, achiral bidentate ligands having 1 or 2 arylcycloalkylphosphine groups and optionally a diarylphosphine group, chiral bidentate ligands having 1 or 2 arylcycloalkylphosphine groups group atoms and optionally a diarylphosphine group and mixtures thereof.

7. The process of any one of the preceding claims, where during the catalytic hydrogenation the molar ratio of the second bidentate phosphorus organic ligand (2) to the rhodium atoms is the range of 0.1 : 1 to 1.0: 1.

8. The process of any one of the preceding claims, where the first bidentate phosphorus organic ligand (1) is present in enantiopure form or has an enantiomeric excess of at least 90% ee.

9. The process of any one of the preceding claims, where the first bidentate phosphorus organic ligand (1) is of the formula (1),Ar— P P— ArI IAr Ar(1)whereRais selected from the group consisting of Ci-Ce-alkyl and Cs-Ce-cycloalkyl; Rbis selected from the group consisting of hydrogen and Ci-Ce-alkyl;orRa, Rbtogether with carbon atoms, to which they are bound form a 5, 6 or 7 membered carbocyclic group, a 6, 7 or 8 membered carbobicyclic group or a 5, 6 or 7 membered heterocyclic group, where the carbocyclic group, the carbobicyclic group and the heterocyclic group are unsubstituted or substituted by 1, 2, 3 or 4 substituents Rcyc, which are selected from Ci-Ce- alkyl, phenyl and benzyl.Ar are identical or different and selected from the group consisting ofCe-Cio-aryl which is unsubstituted or carries one or more substituents which are selected from Ci-Ce-alkyl, Cs-Ce-cycloalkyl, phenyl, Ci-Ce-alkoxy, phenoxy and amino.M / BASFTR-2496-PC10. The process of claim 9, where the first bidentate phosphorus organic ligand (1) is selected from the group consisting of the compounds of the formula (1a) - (1d) and the enantiomers thereof:(1d)11. The process of any one of the preceding claims, where the a,p-unsaturated carbonyl compound is a compound of the formula (V)R5Oin whichR5, R6are different from one another and each is a linear, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more, nonconjugated ethylenic double bonds, and which is unsubstituted or carries one or more identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ce- to Cw-aryl and C3- to Cg-hetaryl;R7is hydrogen or a linear, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more nonconjugated ethylenic double bonds, and which is unsubstituted or carries one or more identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ce- to Cw-aryl and C3- to Cg-hetaryl;M / BASFTR-2496-PCorR7together with one of the radicals R5or R6, can also be a 3- to 25-membered alkylene group, in which 1 , 2, 3 or 4 nonadjacent CH2 groups can be replaced by O or N-R9c, where the alkylene group is saturated or has one or more nonconjugated ethylenic double bonds, and where the alkylene group is unsubstituted or carries one or more identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ci- to C4-alkyl, Ce- to Cw- aryl and C3- to Cg-hetaryl, where two substituents also together can be a 2- to 10-membered alkylene group, where the 2- to 10-membered alkylene group is saturated or has one or more nonconjugated ethylenic double bonds, and where the 2- to 10-membered alkylene group is unsubstituted or carries one or more identical or different substituents which are selected from OR8, NR9aR9b, halogen, Ce- to Cw-aryl and C3- to Cg-hetaryl;whereR8is hydrogen, Ci- to Ce-alkyl, Ce- to Cw-aryl, C7- to Cw-aralkyl or C7- to Cw- alkylaryl;R9a, R9bare in each case independently of one another hydrogen, Ci- to Ce-alkyl, Ce- to Cw-aryl, C7- to Cw-aralkyl or C7- to Cw-alkylaryl, orR9aand R9btogether can also be an alkylene chain having 2 to 5 carbon atoms, which can be interrupted by N or O; andR9cis hydrogen, Ci- to Ce-alkyl, Ce- to Cw-aryl, C7- to Cw-aralkyl or C7- to Cw- alkylaryl.The process of claim 11, where R7is hydrogen.The process of claim 12, where the compound of the formula (V) is represented by one of the following formulae (Va) and (Vb) or a mixture thereof:whereinM / BASFTR-2496-PCR5, R6is in each case a linear or branched hydrocarbon radical having 2 to 25 carbon atoms which is saturated or has 1, 2, 3, 4 or 5 nonconjugated ethylenic double bonds.

14. The process of claim 13, where the compound of the formula (V) is represented by one of the following formulae (Va-1) and (Vb-1) or a mixture thereof:(Va-1) (Vb-1).

15. The process of any one of the preceding claims, which has at least one of the elements 15. a) to 15. d):a) pretreatment of a mixture of the first bidentate chiral phosphorus organic ligand (1) and rhodium and optionally the second bidentate phosphorus organic ligand (2) before the hydrogenation with a gas mixture comprising carbon monoxide and hydrogen;b) the hydrogenation of the a,p-unsaturated carbonyl compound is effected with hydrogen which has a carbon monoxide content in the range from 50 to 3000 ppm, in particular in the range from 100 to 2000 ppm, specifically in the range from 200 to 1000 ppm and very specifically in the range from 400 to 800 ppm; c) the hydrogenation of the a,p-unsaturated carbonyl compound is effected at a hydrogen pressure of from 5 to 200 bar, in particular at a hydrogen pressure of from 10 to 100 bard) the hydrogenation of the a,p-unsaturated carbonyl compound is effected in the presence of a monodentate ligand, which is selected from tertiary phosphines and tertiary amines.

16. A process for the preparation of optically active menthol, comprising the stepsi) preparation of optically active citronellal by asymmetric hydrogenation according to claim 15 from geranial of the formula (Va-1) or from neral of the formula (Vb-1),ii) cyclization of the optically active citronellal prepared in this way to give optically active isopulegol in the presence of a Lewis acid andiii) hydrogenation of the thus prepared optically active isopulegol to give optically active menthol.M / BASFTR-2496-PC17. A catalyst composition comprising rhodium, a first bidentate phosphorus organic ligand (1) having two coordinating phosphorus atoms in the form of diarylphosphine groups and at least one second bidentate phosphorus organic ligand (2) having two coordinating phosphorus atoms, wherein ligand (2) is distinct from ligand (1), wherein the molar ratio of the total amount of ligands (1) and (2) to rhodium is at least 1.8:1, in particular is in the range of 1.8: 1 to 2.5: 1.

18. The catalyst composition of claim 17, wherein the ligand (1) and the ligand (2) are each independently from each other defined according to any one of the preceding claims,preferably wherein ligand (1) is defined as in any one of claims 9 or 10 and ligand (2) is defined as in any one of claims 4 to 6.

19. The catalyst composition of any one of claims 17 or 18, wherein:the molar ratio of ligand (1) to rhodium is in the range of 1.0:1 to 1.7:1, in particular in the range of 1.1 : 1 to 1.6: 1 ; and / orthe molar ratio of ligand (2) to rhodium does not exceed 1:1; and / or wherein ligand (2) comprises two phosphine groups.M / BASFTR-2496-PC

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