FIELD OF THE INVENTION

The invention relates to a process for the synthesis of L-lditol by hydrogenating L-Sorbose in a homogenous catalysed homogenous reaction and to the recycling and reactivation of the stere oselective ruthenium catalyst.

BACKGROUND OF THE INVENTION

L-lditol (CAS Number 488-45-9) is a sugar alcohol which can be derived by conversion of cer tain sugars and carbohydrates. L-lditol can serve, inter alia, as the starting point for the synthe sis of pharmaceuticals, polymers and macrocyclic compounds, but is of particular commercial interest.

As L-lditol is only found in trace amounts in nature, isolation from natural sources is not an eco nomic option. Therefore, the hydrogenation of L-Sorbose (CAS Number: 87-79-6) (produced as an intermediate on a large scale in the vitamin C synthesis) is of particular interest. But in the prior art, only few approaches for accessing L-lditol from L-Sorbose have been suggested.

One way to produce L-lditol is the reduction of L-Sorbose by fermentation with yeasts, as de scribed by M. Ogawa et al. , in Applied and Environmental Microbiology, 1983, 46 (4), 912-916. Unfortunately, the process provides only low yields of L-lditol with a maximum 33% of the con sumed L-Sorbose in the fermentation, because the yeast metabolizes most of the sugar starting material under fermentation conditions. Also isolation of the L-lditol from this mixture was only possible after peracetylation, which must be followed than by a saponification of all acetyl- protecting group, to yield the pure L-lditol in max 27 % yield and resulting in significant amounts of salt-waste from the protection/deprotection sequence.

An improved fermentation of L-Sorbitol to L-lditol using yeasts was reported by V. Vongsuvanlert, J. Ferment. Technol. 1988, 66 (5). Using methanol and xylose as the carbon source for the metabolism increases the yield of L-lditol with regard to the consumed L-Sorbose up to 98 % in the crude fermentation mixture. Unfortunately, this process requires high amounts of FeSCL (1.12 times the amount by weight according the used sorbose) as well as strict pH- Control by using a phosphate buffer. This is a drawback, as the highly water-soluble L-lditol must be separated from the large amount of highly water-soluble salts (which are waste) from the fermentation mixture for isolation of L-lditol. Unfortunately no means for isolation were disclosed. Rather, only the crude fermentation mixture was analyzed by HPLC.

Principally, it should be possible to overcome the drawbacks of a fermentation by heterogene ous hydrogenation of L-Sorbose to L-lditol. For example, EP 0 006 313A1 discloses the produc tion of sugar alcohols by catalytic hydrogenation of keto sugars on copper catalysts containing finely divided metallic copper on a particulate support material. However, applying this process to the reduction of Sorbose yields mainly D-sorbitol. L-lditol can only be obtained as the by product, with a maximum ratio of L-lditol to D-Sorbitol of 38:62 at 100% conversion of L- Sorbose.

There is a demand that the hydrogenation can be run more selectively towards the L-lditol, the whole process would be more efficient, for example there would no longer be a need for the subsequent fermentation as the isolation of L-lditol from the 1: 1-mixture with D-Sorbitol is very difficult and inefficient.

In Angewandte Chemie, International Edition, 2020, DOI: 10.1002/anie.202009790, the hydrogenation of L-Sorbose to L-lditol with a selectivity towards L-lditol >80% using asymmetric transition metal catalysts is described. This approach delivers for the first time in an non- enzymatic process the L-lditol as the main product directly from L-Sorbose without the need for protection groups. However, for an efficient industrial process, a simple recycling of the used expensive stereoselective transition metal catalyst is necessary, which was not disclosed in this work.

A recycling of a stereoselective hydrogenation catalyst without a significiant loss of its activty as well as selectivty is usally not easy to achieve and in most asymmetric transformations, the catalyst is not reused.

Accordingly, it is an object of the invention to provide a process for the recycling and reactiva tion of a stereoselective ruthenium catalyst for the synthesis of L-lditol by hydrogenating L- Sorbose. With this process, it should be possible to produce L-lditol by the hydrogenation of L- Sorbose in a cost-efficient manner.

Surprisingly, it was found that the problem is solved by a process for the preparation of L-lditol comprising at least the process steps: i) a L-Sorbose comprising composition is subjected to hydrogenation with hydrogen in the presence of a hydrophobic stereoselective ruthenium catalyst complex in a homogeneous solution, wherein the ruthenium catalyst complex comprises at least one chiral ligand con taining at least two phosphorus atom, which are capable of coordinating to the ruthenium yielding in a composition comprising L-lditol as the main product; ii) separation of the reaction products produced in step i) from the ruthenium catalyst com plex; iii) reactivating the separated ruthenium catalyst complex of step ii) by adding a chloride source and reusing the reactivated ruthenium catalyst complex in step i).

SUMMARY OF THE INVENTION

The invention relates to a process for the preparation of L-lditol and recycling of the stereose lective catalyst comprising the process steps: 1) a L-Sorbose comprising composition is sub jected to hydrogenation with hydrogen in the presence of a hydrophobic stereoselective ruthe nium catalyst complex in a homogenous solution, wherein the transition metal catalyst complex comprises at least one chiral ligand containing at least two phosphorus atoms, which are capa ble of coordinating to the transition metal yielding in a composition comprising L-lditol as the main product; 2) extraction of the L-lditol and other hexoses with water; 3) Reusing the catalyst in the selective hydrogenation of L-Sorbose to L-lditol under addition of a chloride-source to reactivate the catalyst.

DETAILED DESCRIPTION OF THE INVENTION

The compounds L-Sorbose, L-lditol and D-Sorbitol have the following chemical structions depicted as Fischer projection.

L-Sorbose L-lditol D-Sorbitol

In the context of the invention, the expression "alkyl" means straight and branched alkyl groups. Preferred are straight or branched Ci-C2o-alkyl groups, more preferably CrCi2-alkyl groups, even more preferably CrCs-alkyl groups and in particular CrC ₆ -alkyl groups. Examples of alkyl groups are particularly methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, 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, n-heptyl, 2-heptyl, 3-heptyl, 2-ethylpentyl, 1-propylbutyl, n-octyl, 2-ethyl hexyl, 2-propyl heptyl, nonyl and decyl.

The expression "alkyl" comprises also substituted alkyl groups, which may carry 1, 2, 3, 4 or 5 substituents, preferably 1, 2 or 3 substituents and particularly preferably 1 substituent, selected from the groups cycloalkyl, aryl, hetaryl, halogen, NE ¹ E ² , NE ¹ E ² E ³⁺ , COOH, carboxylate, SO ₃ H and sulfonate. The expression "alkyl" also comprises alkyl groups, which are interrupted by one or more non-adjacent oxygen atoms, preferably alkoxyalkyl.

The expression “alkoxy” in the context of the present invention stands for a saturated, straight- chain or branched hydrocarbon radical having 1 to 4, 1 to 6, 1 to 10, 1 to 20 or 1 to 30 carbon atoms, as defined above, which is bonded via oxygen, e.g. CrC4-alkoxy, such as methoxy, ethoxy, n-propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1- dimethylethoxy; CrC ₆ -alkoxy: CrC4-alkoxy, as specified above, and e.g. pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1 -di methyl propoxy, 1,2-dimethylpropoxy,

2.2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3- methyl pentoxy, 4-methylpentoxy, 1 ,1-dimethylbutoxy, 1 ,2-dimethylbutoxy, 1,3-di ethyl butoxy,

2.2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy,

1.1.2-trimethylpropoxy, 1 ,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2- methylpropoxy.

The expression "alkylene" in the context of the present invention stands for straight or branched alkanediyl groups having 1 to 25, preferably 1 to 6 carbon atoms. These are -CH ₂ -, -(CH ₂ )2-, -(CH ₂ ) ₃ -,-(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -CH(CH ₃ )-, (-CH ₂ -CH(CH ₃ )-), -CH ₂ -CH(CH ₃ )-CH ₂ -, (CH ₂ ) ₄ -, -(CH ₂ ) ₅ -, -(CH ₂ )e, -(CH ₂ ) ₇ -, -CH(CH ₃ )-CH ₂ -CH ₂ -CH(CH ₃ )- or -CH(CH ₃ )-CH ₂ -CH ₂ -CH ₂ - CH(CH ₃ )- etc.

The expression “cycloalkyl” in the context of the present invention stands for a monocyclic, bicyclic or tricyclic, saturated hydrocarbon group having 3 to 12, preferably 3 to 6 or 3 to 8 carbon ring members, e.g. a monocyclic hydrocarbon group having 3 to 8 carbon ring members, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; a bicyclic hydrocarbon group having 5 to 10 carbon ring members, such as bicyclo[2.2.1]hept-1-yl, bicyclo[2.2.1]hept-2-yl, bicyclo[2.2.1]hept-7-yl, bicyclo[2.2.2]oct-1-yl, bicyclo[2.2.2]oct-2-yl, bicyclo[3.3.0]octyl and bicyclo[4.4.0]decyl; a tricyclic hydrocarbon group with 6 to 10 carbon ring members, such as adamantyl.

The expression “cycloalkoxy” (= cycloalkyloxy) in the context of the present invention stands for a monocyclic, bicyclic or tricyclic, saturated hydrocarbon group having 3 to 12, preferably up to 6, up to 8 carbon ring members, as defined above, which is bonded via an oxygen atom.

The expression "heterocycloalkyl" in the context of the present invention comprises saturated or partially unsaturated cycloaliphatic groups with preferably 4 to 7, more preferably 5 or 6 ring atoms, in which 1 , 2, 3 or 4 ring atoms may be substituted with heteroatoms, preferably selected from the elements oxygen, nitrogen and sulfur. The heterocycloalkyl ring is optionally substitut ed. If substituted, these heterocycloaliphatic groups carry preferably 1, 2 or 3 substituents, more preferably 1 or 2 substituents and in particular 1 substituent. These substituents are preferably selected from alkyl, cycloalkyl, aryl, COOR (R = H, alkyl, cycloalkyl, aryl), COOM ⁺ and NE ¹ E ² , more preferably alkyl. Examples of such heterocycloaliphatic groups are pyrrolidinyl, piperidinyl, 2,2,6,6-tetramethylpiperidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, morpholidinyl, thiazoli- dinyl, isothiazolidinyl, isoxazolidinyl, piperazinyl, tetrahydrothiophenyl, tetrahydrofuranyl, tetra- hydropyranyl and dioxanyl. The expression "aryl" in the context of the present invention comprises a mono- or polynuclear aromatic hydrocarbon radical having usually 6 to 14, preferably 6 to 10 carbon atoms, such as e.g. phenyl, tolyl, xylyl, mesityl, naphthyl, indenyl, fluoroenyl, anthracenyl or phenanthrenyl. In case these aryl groups are substituted, they may carry preferably 1, 2, 3, 4 or 5 substituents, more preferably 1 , 2 or 3 substituents and particularly preferred 1 substituent. These substitu ents are preferably selected from the groups alkyl, alkoxy, carboxyl, carboxylate, trifluoromethyl, -SO ₃ H, sulfonate, NE ¹ E ² , alkylene-NE ¹ E ² , nitro, cyano and halogen. A preferred fluorinated aryl group is pentafluorophenyl.

The expression “aryloxy” in the context of the present invention stands for a mono- or polynuclear aromatic hydrocarbon radical having usually 6 to 14, preferably 6 to 10 carbon atoms, as defined above, which is bonded via an oxygen atom.

The expression “heterocycloalkyl (= heterocyclyl) with 3 to 12 ring atoms” in the context of the present invention refers to a saturated, partially (e.g. mono-) unsaturated heterocyclic radical having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, of which 1, 2 or 3 are selected from N, O, S, S(O) and S(0) ₂ , and the other ring atoms are carbon, such as e.g. 3- to 8-membered saturated heterocyclyl, such as oxiranyl, oxetanyl, aziranyl, piperidinyl, piperazinyl, morpholinyl, thimorpholinyl, pyrrolidinyl, oxazolidinyl, tetrahydrofuryl, dioxolanyl, dioxanyl, hexahydroazepinyl, hexyhydrooxepinyl, and hexahydrothiepinyl; partially unsaturated 3-, 4-, 5-, 6-, 7- or 8-membered heterocyclyl, such as di- and tetrahydropyridinyl, pyrrolinyl, oxazolinyl, dihydrofuryl, tetrahydroazepinyl, tetrahydrooxepinyl, and tetrahydrothiepinyl.

The expression “heterocycloalkoxy (= heterocycloalkoxy) with 3 to 12 ring atoms” in the context of the invention is a saturated, partially (e.g. mono-) unsaturated heterocyclic radical having 3,

4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, of which 1, 2 or 3 are selected from N, O, S, S(O) and S(0) ₂ , and the other ring atoms are carbon, as defined above, which is bonded via oxygen.

The expression “hetaryl (= heteroaryl)” in the context of the invention is an aromatic, mono- or polynuclear heterocycle, which, besides carbon atoms, comprises one to four heteroatoms from the group O, N or S as ring members, such as e.g.

5-membered heteroaryl, which, besides carbon atom(s), can comprise one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom or one sulfur or oxygen atom as ring member, e.g. furyl, thienyl, pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl; benzo-fused 5-membered heteroaryl: 5-ring heteroaryl groups as defined above, which may be condensed with one or two benzene rings in such a way that two adjacent carbon ring members or one nitrogen and one adjacent carbon ring member are bridged by a buta-1,3-diene-1,4-diyl group, e.g. indolyl, isoindolyl, benzimidazolyl, benzofuryl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, dibenzofuranyl, dibenzothienyl or carbazolyl;

6-membered heteroaryl: 6-ring heteroaryl groups, which, besides carbon atoms, can comprise one to three or one to four nitrogen atoms as ring members, e.g. pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazin-2-yl and 1,2,4-triazin-3-yl; benzo-fused 6-membered heteroaryl: 6-ring heteroaryl groups as defined above, which may be condensed with one or two benzene rings in such a way that two adjacent carbon ring members are bridged by a buta-1,3-diene-1,4-diyl group, e.g. quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, acridinyl or phenazinyl.

If these heterocycloaromatic groups are substituted, they may carry preferably 1, 2 or 3 substit uents selected from the groups alkyl, alkoxy, carboxyl, carboxylate, -SO ₃ H, sulfonate, NE ¹ E ² , alkylene-NE ¹ E ² , trifluoromethyl and halogen.

Carboxylate and sulfonate in the context of the present invention preferably stand for a deriva tive of a carboxylic acid function or a sulfonic acid function, in particular a metal carboxylate or metal sulfonate, a carboxylic acid ester or sulfonic acid ester or a carboxylic acid amide or sul fonic acid amide. Particularly preferred are esters with CrC4-alkanols like methanol, ethanol, n- propanol, isopropanol, n-butanol, sec-butanol and tert-butanol. Preferred are also the primary amides and their N-alkyl and N,N-dialkyl derivatives.

The expression "acyl" in the context of the present invention stands for alkanoyl groups or aroyl groups with preferably 2 to 11 , more preferably 2 to 8 carbon atoms, for example acetyl, propa- noyl, butanoyl, pentanoyl, hexanoyl, heptanoyl, 2-ethyl hexanoyl, 2-propylheptanoyl, benzoyl and naphthoyl.

The groups NE ¹ E ² , NE ⁴ E ⁵ and NE ⁷ E ⁸ are preferably selected from N,N-dimethylamino, N,N- diethylamino, N,N-dipropylamino, N,N-diisopropylamino, N,N-di-n-butylamino, N,N-di-tert- butylamino, N,N-dicyclohexylamino and N,N-diphenylamino.

Halogen stands for fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine. Formyl ist H-C(=0)-. Carboxy is -C(=0)0H. Sulfo is -S(=0) ₂ -0H.

Polyalkylene oxide is a radical derived from identical or different C2-4-oxyalkylene monomer building blocks, as defined above, with a degree of polymerization (number average) in the range of 2 to 100, or 3 to 50 or 4 to 25 or 5 to 10.

Polyalkyleneimine is a structure-analogous radical to the above polyalkylene oxide radical with the oxygen atom being replaced by an imine group.

M ⁺ refers to a cation equivalent, which means a monovalent cation or the part of a polyvalent cation representing a positive single charge. The cation M ⁺ is only a counter ion, which neutral izes negatively charged substituents like the COO or the sulfonate group and which can princi pally be selected arbitrarily. Preferred are alkaline metal ions, in particular Na ⁺ , K ⁺ and Li ⁺ ions, or onium ions like ammonium ions, mono-, di-, tri-, tetraalkylammonium ions, phosphonium ions, tetraalkylphosphonium ions and tetraarylphosphonium ions.

The same applies to the anion equivalent X-, which is only a counter ion for positively charged substituents like the ammonium group and which can principally be selected arbitrarily among monovalent anions and the parts of polyvalent anions, which correspond to a single negative charge. Preferred are halogenides X-, in particular chloride and bromide. Also preferred are sul fates and sulfonates, in particular SO4 ^2' , tosylate, trifluoromethane sulfonate and methyl- sulfonate.

Condensed ring systems, also termed fused ring systems, are aromatic, heteroaromatic or cy clic compounds, which have fused-on rings obtained via anellation. Condensed ring systems consist of two, three or more than three rings. Depending on the type of connection, one distin guishes between ortho-anellation and peri-anellation. In case of ortho-anellation, each ring has two atoms in common with each adjacent ring. In case of peri-anellation, a carbon atom belongs to more than two rings. Preferred among the condensed ring systems are ortho-condensed ring systems.

In the context of the present invention, "chiral ligands" are ligands without an axis of symmetry. They are in particular ligands with at least one chirality center (i.e. at least one asymmetric atom, in particular at least one asymmetric P atom or C atom). In a special embodiment of the present invention, addition ligands are employed, which show axial chirality. Axial chirality occurs, for example, in biphenyls, such as BINAP, which are substituted in the ortho-positions in such a way that the free rotation of the aromatic compounds around the C-C single bond is strongly hindered. This then results in two mirror-image isomers.

In the context of the present invention, the term "chiral catalyst" comprises catalysts, which have at least one chiral ligand.

"Achiral compounds" are compounds, which are not chiral.

A "prochiral compound" is understood as meaning a compound with at least one prochiral center.

"Asymmetric synthesis" refers to a reaction in which a compound with at least one chirality center is produced from a compound with at least one prochiral center, where the stereoisomeric products are formed in unequal amounts.

"Stereoisomers" are compounds of identical constitution, but different atomic arrangement in the three-dimensional space.

"Enantiomers" are stereoisomers, which behave like image to mirror image to one another. The “enantiomeric excess” (ee) achieved during asymmetric synthesis is given here by the following formula: ee [%] = (R-S)/(R+S) x 100. R and S are the descriptors of the CIP system for the two enantiomers and describe the absolute configuration on the asymmetric atom. The enantiomerically pure compound (ee = 100%) is also referred to as “homochiral compound”.

The process according to the invention leads to products, which are enriched with regard to a specific stereoisomer, in particular with regard to L-lditol. The attained “enantiomer excess” (ee) is generally at least 20%, preferably at least 50%, in particular at least 80%.

"Diastereomers" are stereoisomers, which are not enantiomeric to one another.

Starting material

L-Sorbose is commercially available or can be prepared from D-Sorbitol via microbiological oxi dation. Process step i):

Catalyst

In the process of the invention, the composition comprising L-Sorbose is subjected to hydrogenation in a liquid reaction medium in the presence of a transition metal catalyst complex, which comprises at least one chiral ligand containing at least two phosphorus atoms, which are capable of coordinating to the transition metal and ruthenium as the metal center.

Due to this chiral ligand the transition metal catalyst complex is stereoselective. In other words: Applying the stereoselective transition metal catalyst complex the product mixture predominately comprises the desired stereoisomer. In particular, the product mixture exclusively comprises the desired stereoisomer.

The process of the invention is carried out as a homogeneously catalyzed hydrogenation using a ruthenium catalyst complex. That means the ruthenium catalyst complex is dissolved in the liquid reaction medium under the reaction conditions. Typically, the ruthenium catalyst complex is in the same phase as the reactants, i.e. the L-Sorbose. Further, the liquid reaction medium may comprise at least one chiral ligand in excess. In this embodiment, the liquid reaction con tains free chiral ligands that are not bound to the ruthenium complex. The free chiral ligands are selected from the phosphorous containing ligands defined in the following.

The ruthenium catalyst complex comprises at least one chiral ligand containing at least two phosphorus atoms, which are capable of coordinating to the transition metal. Typically, the mo lar ratio of the chiral ligand to the transition metal is at least 1, e.g. in the range from 1 to 4, es pecially 1 or 2. The chiral ligand contains at least two phosphorus atoms, which are capable of coordinating to the transition metal and is especially a chiral bidentate ligand having two phos phorous atoms, which are capable of coordinating to the ruthenium. More particularly, the ru thenium catalyst complex has 1 or 2 chiral bidentate ligands having two phosphorous atoms, which are capable of coordinating to the transition metal, in particular 1 of such a bidentate chi ral ligand. Especially, the ruthenium catalyst complex has 1 or 2 chiral bidentate ligands having two phosphorous atoms, which are capable of coordinating to the transition metal, in particular 1 of such a bidentate chiral ligand.

According to the invention, the ligand containing at least two phosphorus atoms, which are ca pable of coordinating to the transition metal, is chiral, i.e. it bears at least one group that is asymmetric. Chirality of the ligand may be caused, e.g. because at least one of the P atoms is asymmetric, and/or the ligand has axial chirality. In particular, the chiral ligand bears a group, which causes axial chirality.

Preferably, the chiral ligand is selected from compounds of formula (I) wherein

R ^A , R ^B , R ^c and R ^D are independently from each other selected from the group consisting of alkyl having in particular 1 to 30 carbon atoms, cycloalkyl having in particular 3 to 12 carbon ring members, heterocycloalkyl having in particular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, and hetaryl having in particular 5 to 14 ring atoms, wherein the alkyl radicals may be unsubstituted or carry 1, 2, 3, 4 or 5 substituents selected from cycloalkyl having in particular 5 to 8 carbon ring members, heterocycloalkyl having in par ticular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, hetaryl having in particular 5 to 14 ring at oms, alkoxy having in particular 1 to 4 carbon atoms, cycloalkoxy having in particular 5 to 8 car bon ring members, heterocycloalkoxy having in particular 3 to 12 ring atoms, aryloxy, such as C6-Ci4-aryloxy, hetaryloxy having in particular 5 to 14 ring atoms, hydroxy, mercapto, poly- alkylene oxide, polyalkyleneimine, carboxyl, SO ₃ H, sulfonate, NE ¹ E ² , NE ¹ E ² E ³⁺ X , halogen, ni- tro, formyl, acyl and cyano, wherein E ¹ , E ² and E ³ are the same or different and are selected from hydrogen, alkyl, such as CrC2o-alkyl, cycloalkyl having in particular 3 to 12 carbon ring members, and aryl, such as Ce-Cu-aryl, and X- is an anion equivalent, and wherein the radicals cycloalkyl, heterocycloalkyl, aryl and hetaryl in R ^A , R ^B , R ^c and R ^D may be unsubstituted or carry 1 , 2, 3, 4 or 5 substituents selected from alkyl having in particular 1 to

4 carbon atoms, cycloalkyl having in particular 5 to 8 carbon ring members, heterocycloalkyl having in particular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, hetaryl having in particular 5 to 14 ring atoms, alkoxy having in particular 1 to 10 carbon atoms, cycloalkoxy having in particular

5 to 8 carbon ring members, heterocycloalkoxy having in particular 3 to 12 ring atoms, aryloxy, such as C6-Ci4-aryloxy, hetaryloxy having in particular 5 to 14 ring atoms, hydroxy, mercapto, polyalkylene oxide, polyalkyleneimine, carboxyl, SO ₃ H, sulfonate, NE ¹ E ² , NE ¹ E ² E ³⁺ X ^_ , halogen, nitro, formyl, acyl and cyano, or R ^A and R ^B and/or R ^c and R ^D together with the P atom and, if present, the groups X ¹ , X ² , X ⁵ and X ⁶ to which they are bound, are a 5- to 8-membered heterocycle, which is optionally fused with one, two or three groups selected from cycloalkyl having in particular 5 to 8 carbon ring mem bers, heterocycloalkyl having in particular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, hetaryl having in particular 5 to 14 ring atoms, wherein the heterocycle and, if present, the fused-on groups independently from each other may each carry 1 , 2, 3 or 4 substituents selected from alkyl having in particular 1 to 10 carbon atoms, cycloalkyl having in particular 5 to 8 carbon ring members, heterocycloalkyl having in particular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, he taryl having in particular 5 to 14 ring atoms, hydroxy, mercapto, polyalkylene oxide, poly- alkyleneimine, alkoxy, halogen, carboxyl, SO ₃ H, sulfonate, NE ⁴ E ⁵ , NE ⁴ E ⁵ E ⁶⁺ X ^_ , nitro, alkoxycar- bonyl, such as Ci-C20-alkoxycarbonyl, formyl, acyl and cyano, wherein E ⁴ , E ⁵ and E ⁶ are the same or different and are selected from hydrogen, alkyl, such as CrC2o-alkyl, cycloalkyl having in particular 3 to 12 carbon ring members and aryl, such as Ce-Cu-aryl, and X- is an anion equivalent,

X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸ and X ⁹ are independently from each other O, S, CR ^x R ^y , SiR ^x R ^y or NR ^Z , wherein R ^x , R ^y and R ^z are independently from each other hydrogen, alkyl having in particu lar 1 to 4 carbon atoms, cycloalkyl having in particular 5 to 8 carbon ring members, heterocyclo alkyl having in particular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, or hetaryl having in partic ular 5 to 14 ring atoms,

Y is a divalent bridging group, which contains carbon atoms, a, b, c, d, e and f are independently from each other 0 or 1, provided that formula (I) has at least one chiral group, e.g. because at least one of the P atoms is asymmetric, and/or the ligand of formula (I) has axial chirality.

In formula (I), the variables R ^A , R ^B , R ^c , R ^D , X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸ , X ⁹ , a, b, c, d, e and f, individually or in particular in combination, have preferably the following meanings, provided that formula (I) has at least one chiral group, e.g. because at least one of the P atoms is asymmet ric, and/or the ligand of formula (I) has axial chirality:

R ^A , R ^B , R ^c and R ^D , are independently from each other Ci-C3o-alkyl, C3-Ci2-cycloalkyl, heterocy cloalkyl with 3 to 12 ring atoms, Ce-Cu-aryl or hetaryl with 5 to 14 ring atoms, wherein the alkyl radical may carry 1 , 2, 3, 4 or 5 substituents selected from C3-Ci2-cycloalkyl, heterocycloalkyl with 3 to 12 ring atoms, Ce-Cu-aryl, hetaryl with 5 to 14 ring atoms, C1-C10- alkoxy, C3-Ci2-cycloalkoxy, heterocycloalkoxy with 3 to 12 ring atoms, Ce-Cu-aryloxy, he- taryloxy with 5 to 14 ring atoms, hydroxy, mercapto, polyalkylene oxide, polyalkyleneimine, car boxyl, SO ₃ H, sulfonate, NE ¹ E ² , NE ¹ E ² E ³⁺ X ^_ , halogen, nitro, formyl, acyl and cyano, wherein E ¹ , E ² and E ³ are the same or different and are selected from hydrogen, Ci-C2o-alkyl, C3-C12- cycloalkyl, and Ce-Cu-aryl and X ^_ is an anion equivalent, and wherein the radicals cycloalkyl, heterocycloalkyl, aryl and hetaryl radicals may carry 1 , 2, 3, 4 or 5 substituents selected from CrC2o-alkyl and the substituents mentioned for the alkyl radi cal R ^A , R ^B , R ^c and R ^D before, or

R ^A and R ^B and/or R ^c and R ^D together with the P atom and, if present, the groups X ¹ , X ² , X ⁵ and X ⁶ to which they are bound, are a 5- to 8-membered heterocycle, which is optionally fused with one, two or three groups selected from C3-Ci2-cycloalkyl, heterocycloalkyl with 3 to 12 ring at oms, Ce-Cu-aryl and heteroaryl with 5 to 14 ring atoms, wherein the heterocycle and, if present, the fused-on groups independently from each other may each carry 1, 2, 3 or 4 substituents selected from Ci-C2o-alkyl, C3-Ci2-cycloalkyl, heterocycloalkyl with 3 to 12 ring atoms, Ce-Cu- aryl, hetaryl with 5 to 14 ring atoms, hydroxy, mercapto, polyalkylene oxide, polyalkyleneimine, CrC2o-alkoxy, halogen, carboxyl, SO ₃ H, sulfonate, NE ⁴ E ⁵ , NE ⁴ E ⁵ E ⁶⁺ X , nitro, alkoxycarbonyl, such as C1-C20 alkoxycarbonyl, formyl, acyl and cyano, wherein E ⁴ , E ⁵ and E ⁶ are the same or different and are selected from hydrogen, CrC2o-alkyl, C3-Ci2-cycloalkyl and Ce-Cu-aryl and X- is an anion equivalent,

X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸ and X ⁹ are independently from each other O, S, CR ^x R ^y , SiR ^x R ^y or NR ^Z , wherein R ^x , R ^y and R ^z are independently from each other hydrogen, CrC2o-alkyl, C3-C12- cycloalkyl, heterocycloalkyl with 3 to 12 ring atoms, C ₆ -Cu-aryl or hetaryl with 5 to 14 ring at oms,

Y is a divalent bridging group, which contains carbon atoms, a, b, c, d, e and f are independently from each other 0 or 1.

In particular, the chiral ligand is selected from organo phosphines, in particular from compounds of the formula (I), wherein a, b, c, d, e and f are 0, or wherein X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸ and X ⁹ are, at each occurrence, a group CR ^x R ^y . In particular, the integers a, b, c, d, e and f in formula (I) are 0. In formula (I), the variables R ^A , R ^B , R ^c , R ^D have in particular the following meanings:

R ^A , R ^B , R ^c and R ^D are independently from each other selected from the group consisting of alkyl having in particular 1 to 30 carbon atoms, aryl, such as Ce-Cu-aryl or heteroaryl, having in par ticular 5 to 14 ring atoms, wherein the alkyl radical may carry 1, 2, 3, 4 or 5 substituents select ed from alkoxy, such as CrCs-alkoxy, NE ¹ E ² ,

NE ¹ E ² E ³⁺ X , wherein E ¹ , E ² and E ³ are the same or different and are selected from hydrogen or alkyl, and X- is an anion equivalent, and the aryl or heteroaryl radicals may carry 1 , 2, 3, 4 or 5 substituents selected from the group consisting of alkyl having in particular 1 to 8 carbon atoms, alkoxy having in particular 1 to 8 carbon atoms, NE ¹ E ² and NE ¹ E ² E ³⁺ X\

More particularly, the variables R ^A , R ^B , R ^c , R ^D have in particular the following meanings:

Organo phosphines are derived from phosphines (also called phosphanes), wherein one or more hydrogens are replaced by an organic substituent.

In particular, the chiral ligand is selected from compounds of formulae (II) or (III) wherein,

R ^A , R ^B , R ^c and R ^D have one of the meanings as defined above, and wherein R ^A , R ^B , R ^c and R ^D are in particular, independently of each other, selected from the group consisting of alkyl having in particular 1 to 30 carbon atoms, aryl, such as Ce-Cu-aryl or heteroaryl having in particular 5 to 14 ring atoms, wherein the alkyl radical may carry 1 , 2, 3, 4 or 5 substituents selected from alkoxy, such as CrCs-alkoxy, NE ¹ E ² , NE ¹ E ² E ³⁺ X , wherein E ¹ , E ² and E ³ are the same or different and are selected from hydrogen or alkyl, and X- is an anion equivalent, and the aryl or heteroaryl radicals may carry 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl having in particular 1 to 8 carbon atoms, alkoxy having in par ticular 1 to 8 carbon atoms, NE ¹ E ² and NE ¹ E ² E ³⁺ X ^_ ;

Y is a divalent bridging group, which contains carbon atoms,

Q ¹ , Q ² and Q ³ are independently from each other a divalent bridging group of the formula (IV), wherein

# denotes the binding sites to the remainder of the molecule,

R ^e1 , R ^e2 , R ^e3 , R ^e4 , R ^e5 , R ^e6 , R ^e7 and R ^e8 are independently from each other selected from the group consisting of hydrogen, in each case unsubstituted or substituted alkyl having in particular 1 to 20 carbon atoms, alkoxy having in particular 1 to 20 carbon atoms, cycloalkyl having in par ticular 3 to 12 carbon atoms, cycloalkoxy having in particular 3 to 12 carbon atoms, heterocy cloalkyl having in particular 3 to 12 ring atoms, heterocycloalkoxy having in particular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, aryloxy, such as Ce-Cu-aryloxy, hetaryl having in particular 5 to 14 ring atoms, hetaryloxy having in particular 5 to 14 ring atoms, halogen, hydroxy, mercapto, cyano, nitro, formyl, acyl, carboxy, carboxylate, C1-C20- alkylcarbonyloxy, carbamoyl, SO ₃ H, sulfonate or NE ⁷ E ⁸ , wherein E ⁷ and E ⁸ are the same or dif ferent and are selected from hydrogen, alkyl, such as Ci-C2o-alkyl, cycloalkyl having in particular 3 to 12 carbon ring members, heterocycloalkyl having in particular 3 to 12 ring member atoms, aryl, such as Ce-Cu-aryl, and hetaryl having in particular 5 to 14 ring member atoms, wherein two adjacent radicals R ^e1 to R ^e8 together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system with 1, 2 or 3 further rings, and A ¹ is a single bond, O, S, NR ^a31 , SiR ^a32 R ^a33 or CrC4-alkylene, which may have a double bond and/or which may be substituted with alkyl, such as CrC2o-alkyl, cycloalkyl having in particular 3 to 12 carbon ring members, heterocycloalkyl having in particular 3 to 12 ring member atoms, aryl, such as Ce-Cu-aryl, and hetaryl having in particular 5 to 14 ring member atoms, or which may be interrupted by O, S, NR ^a31 or SiR ^a32 R ^a33 , wherein R ^a31 , R ^a32 and R ^a33 are independently from each other hydrogen, alkyl, such as CrC2o-alkyl, cycloalkyl having in particular 3 to 12 carbon ring members, heterocycloalkyl having in particular 3 to 12 ring member atoms, aryl, such as Ce-Cu-aryl, and hetaryl having in particular 5 to 14 ring member atoms; provided that formulae (II) and (III) have at least one chiral group, e.g. because at least one of the P atoms in formulae (II) and (III) is asymmetric and/or the ligands of formulae (II) and (III) have axial chirality.

More particularly, the chiral ligand is selected from compounds of formulae (II) or (III) wherein

R ^A , R ^B , R ^c and R ^D have one of the meanings as defined above, and wherein R ^A , R ^B , R ^c and R ^D are in particular, independently of each other, selected from the group consisting of alkyl having in particular 1 to 30 carbon atoms, aryl, such as Ce-Cu-aryl, or heteroaryl having in particular 5 to 14 ring atoms, wherein the alkyl radical may carry 1 , 2, 3, 4 or 5 substituents selected from alkoxy, such as CrCs-alkoxy, NE ¹ E ² , NE ¹ E ² E ³⁺ X ^_ , wherein E ¹ , E ² and E ³ are the same or different and are selected from hydrogen or alkyl, and X- is an anion equivalent, and the aryl or heteroaryl radicals may carry 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl having in particular 1 to 8 carbon atoms, alkoxy having in par ticular 1 to 8 carbon atoms, NE ¹ E ² and NE ¹ E ² E ³⁺ C ^_ ; Y is a divalent bridging group, which contains carbon atoms,

Q ¹ , Q ² and Q ³ are independently from each other a divalent bridging group of the formula (IV), wherein

# denotes the binding sites to the remainder of the molecule,

R ^e1 , R ^e2 , R ^e3 , R ^e4 , R ^e5 , R ^e6 , R ^e7 and R ^e8 are independently from each other hydrogen, in each case unsubstituted or substituted CrC2o-alkyl, CrC2o-alkoxy, C3-Ci2-cycloalkyl, C3-C12- cycloalkoxy, heterocycloalkyl with 3 to 12 ring atoms, heterocycloalkoxy with 3 to 12 ring atoms, C6-Ci4-aryl, Ce-Cu-aryloxy, hetaryl with 5 to 14 ring atoms, hetaryloxy with 5 to 14 ring atoms; halogen, hydroxy, mercapto, cyano, nitro, formyl, acyl, carboxy, carboxylate, C1-C20- alkylcarbonyloxy, carbamoyl, SO ₃ H, sulfonate or NE ⁷ E ⁸ , wherein E ⁷ and E ⁸ are the same or dif ferent and are selected from hydrogen, CrC2o-alkyl, C3-Ci2-cycloalkyl, heterocycloalkyl with 3 to 12 ring atoms, Ce-Cu-aryl and hetaryl with 5 to 14 ring atoms, wherein two adjacent radicals R ^e1 to R ^e8 together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system with 1, 2 or 3 further rings, and

A ¹ is a single bond, O, S, NR ^a31 , SiR ^a32 R ^a33 or

CrC4-alkylene, which may have a double bond and/or CrC4-alkylene which may be substituted with CrC2o-alkyl, C3-Ci2-cycloalkyl, heterocycloalkyl with 3 to 12 ring atoms, Ce-Cu-aryl or he taryl with 5 to 14 ring atoms or CrC4-alkylene which may be interrupted by O, S, NR ^a31 or Si- R ^a32 R ^a33 wherein R ^a31 , R ^a32 and R ^a33 are independently from each other hydrogen, CrC2o-alkyl, C3-Ci2-cycloalkyl, heterocycloalkyl with 3 to 12 ring atoms, Ce-Cu-aryl or hetaryl with 5 to 14 ring atoms, provided that formulae (II) and (III) have at least one chiral group, e.g. because at least one of the P atoms in formulae (II) and (III) is asymmetric and/or the ligands of formulae (II) and (III) have axial chirality.

In formula (IV), the radicals R ^e1 , R ^e2 , R ^e3 , R ^e4 , R ^e5 , R ^e6 , R ^e7 and R ^e8 are preferably independently from each other selected from the group consisting of hydrogen, halogen in each case unsubsti tuted or substituted Ci-Cio-alkyl, CrCio-alkoxy, Ce-Cu-aryl, hetaryl with 5 to 10 atoms, or two adjacent radicals R ^e1 to R ^e8 together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system with one further ring, and in formula (IV) the radical A ¹ is in particular a single bond, O or S.

In a very preferred group of embodiments, the transition metal catalyst complex comprises at least one chiral ligand selected from compounds of formulae (I) or (II), wherein

R ^A , R ^B , R ^c and R ^D are independently from each other alkyl having in particular 1 to 30 carbon atoms, aryl, such as Ce-Cu-aryl, or heteroaryl having in particular 5 to 14 ring atoms, wherein the alkyl radical may carry 1, 2, 3, 4 or 5 substituents selected from alkoxy, NE ¹ E ² , NE ¹ E ² E ³⁺ X , wherein E ¹ , E ² and E ³ are the same or different and are selected from hydrogen or alkyl having in particular 1 to 10 carbon atoms, and X- is an anion equivalent, and wherein the aryl or het eroaryl radicals may carry 1, 2, 3, 4 or 5 substituents selected from alkyl, alkoxy, NE ¹ E ² , NE ¹ E ² E ³⁺ X , wherein E ¹ , E ² and E ³ are the same or different and are selected from hydrogen or alkyl having in particular 1 to 10 carbon atoms, and X- is an anion equivalent,

Y is a divalent bridging group, which contains carbon atoms, and a, b, c, d, e and f are independently from each other 0, provided that formulae (I) and (II) have at least one chiral group, e.g. because at least one of the P atoms in formulae (I) and (II) is asymmetric, and/or the ligands of formulae (I) and (II) have axial chirality.

Even more preferably, the transition metal catalyst complex comprises at least one chiral ligand selected from compounds of formulae (I) or (II), wherein

R ^A , R ^B , R ^c and R ^D are independently from each other CrCio-alkyl, C6-Ci2-aryl or heteroaryl with 5 to 10 ring atoms, wherein the alkyl radical may carry 1 , 2, 3, 4 or 5 substituents selected from CrCio-alkoxy, NE ¹ E ² , NE ¹ E ² E ³⁺ X , wherein E ¹ , E ² and E ³ are the same or different and are se lected from hydrogen or CrCio-alkyl, and X- is an anion equivalent, and wherein the aryl or het eroaryl radicals may carry 1, 2, 3, 4 or 5 substituents selected from CrCio-alkyl, CrCio-alkoxy, NE ¹ E ² , NE ¹ E ² E ³⁺ X , wherein E ¹ , E ² and E ³ are the same or different and are selected from hy drogen or CrCio-alkyl, and X- is an anion equivalent,

Y is a divalent bridging group, which contains carbon atoms, and a, b, c, d, e and f are independently from each other 0, provided that formulae (I) and (II) have at least one chiral group, e.g. because at least one of the P atoms in formulae (I) and (II) is asymmetric, and/or the ligands of formulae (I) and (II) have axial chirality.

Especially, the transition metal catalyst complex comprises at least one ligand selected from compounds of formulae (I) or (II), wherein

R ^A , R ^B , R ^c and R ^D are C6-Ci2-aryl, especially phenyl, which may carry 1 , 2, 3, 4 or 5 substituents selected from CrCio-alkyl and CrCio-alkoxy,

Y is a divalent bridging group, which contains carbon atoms, and a, b, c, d, e and f are independently from each other 0, provided that formulae (I) and (II) have at least one chiral group, e.g. because at least one of the P atoms in formulae (I) and (II) is asymmetric, and/or the ligands of formulae (I) and (II) have axial chirality.

As mentioned above, the chiral ligand either contains at least one chirality center or exhibit axial chirality.

In a preferred embodiment, the chiral ligand exhibits axial chirality. Especially, the ligands of formulae (I), (II) and (III) have axial chirality. Especially, axial chirality is caused by the bridging group Y.

Preferably, the divalent bridging group Y in formulae (I), (II) and (III) is selected from groups of the formulae (V) or (VI): wherein

# denotes the binding sites to the remainder of the molecule,

R ¹ , R ^1' , R", R" ^' , R ¹ ", R ¹ " ^' , R ^IV , R ^IV' , R ^v , R ^v' , R ^VI , R ^VI' , R ^v ", R ^VI " ^' , R ^VI ", R ^IX , R ^x , R ^XI and R ^x " are each, independently from each other, hydrogen, alkyl having in particular 1 to 20 carbon atoms, cy cloalkyl having in particular 3 to 12 carbon ring members, heterocycloalkyl having in particular 3 to 12 ring atoms, aryl, such as Ce-Cu-aryl, and hetaryl having in particular 5 to 14 ring atoms, hydroxy, thiol, polyalkylene oxide, polyalkylenimine, alkoxy, halogen, SO ₃ H, sulfonate, NE ¹ E ² , alkylene-NE ¹ E ² , nitro, alkoxycarbonyl, carboxyl, acyl or cyano, wherein E ¹ and E ² are as defined above and in particular selected from the group consisting of hydrogen, alkyl having in particular 1 to 20 carbon atoms, cycloalkyl having in particular 3 to 12 carbon ring members and aryl, such as Ce-Cu-aryl, wherein two adjacent radicals R ^1' , R ^11' , R ^111' , R ^IV , R ^v' , R ^vr , R ^vm' together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system with 1, 2 or 3 further rings, wherein the ring atoms are selected from carbon, oxygen and sulfur, and wherein each of the rings may carry 1, 2 or 3 substituents selected from halogen, CrC4-alkyl and C1-C4- alkoxy, wherein two radicals R ^IV and R ^v together with the carbon atoms of the two benzene rings to which they are bound may also be a condensed ring system, wherein the ring atoms are select ed from carbon, oxygen and sulfur, and wherein each of the rings may carry 1, 2 or 3 substitu ents selected from halogen CrC4-alkyl and Ci-C4-alkoxy.

More preferably, the divalent bridging group Y has one of the meanings of formulae (V) or (VI) wherein

# denotes the binding sites to the remainder of the molecule,

R ¹ , R ^1' , R", R ^11' , R ¹¹¹ , R ^111' , R ^IV , R ^IV' , R ^v , R ^v' , R ^VI , R ^VI' , R ^v ", R ^VI " ^' , R ^VI ", R ^IX , R ^x , R ^XI and R ^x " are each, independently from each other, hydrogen, CrC2o-alkyl, C3-Ci2-cycloalkyl, heterocycloalkyl with 3 to 12 ring atoms, Ce-Cu-aryl, hetaryl with 5 to 14 ring atoms, hydroxy, thiol, polyalkylene ox ide, polyalkylenimine, CrC2o-alkoxy, halogen, SO ₃ H, sulfonate, NE ¹ E ² , alkylene-NE ¹ E ² , nitro, CrC20-alkoxycarbonyl, carboxyl, acyl or cyano, wherein E ¹ and E ² are identical or different and are selected from hydrogen, CrC2o-alkyl, C3-Ci2-cycloalkyl and Ce-Cu-aryl, wherein two adjacent radicals R ^1' , R" ^' , R ^m' , R ^IV , R ^v' , R ^vr , R ^vm' together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system with 1, 2 or 3 further rings, wherein the ring atoms are selected from carbon, oxygen and sulfur, and wherein each of the rings may carry 1, 2 or 3 substituents selected from halogen, CrC4-alkyl and C1-C4- alkoxy, wherein two radicals R ^IV and R ^v together with the carbon atoms of the two benzene rings to which they are bound may also be a condensed ring system, wherein the ring atoms are select ed from carbon, oxygen and sulfur, and wherein each of the rings may carry 1, 2 or 3 substitu ents selected from halogen CrC4-alkyl and Ci-C4-alkoxy.

Especially, the radicals R', R ^r , R", R" ^' , R ^m , R'" ^' , R ^IV , R ^IV’ , R ^v , R ^v , R ^VI , R ^vr , R ^v ", R ^vm' , R ^vm , R ^IX , R ^x , R ^XI and R ^XM are each, independently from each other, hydrogen, Ci-Cio-alkyl, C6-Ci2-aryl, hetar- yl with 5 to 10 atoms, wherein two adjacent radicals R ^1' , R ^11' , R ^111' , R ^IV , R ^v' , R ^vr , R ^vm' together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system with 1, 2 or 3 further rings, wherein the ring atoms are selected from carbon, oxygen and sulfur, and wherein the each of the rings may carry 1, 2 or 3 substituents selected from halogen, CrC4-alkyl and Cr C4-alkoxy, wherein two radicals R ^IV and R ^v together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system, wherein the ring atoms are selected from carbon, oxygen and sulfur, and wherein each of the rings may carry 1 , 2 or 3 substituents se lected from halogen CrC4-alkyl and Ci-C4-alkoxy.

Especially, the divalent bridging group Y has one of the meanings of formulae (V), wherein R ¹ , R ^1' , R", R ^11' , R ^m , R ^111' , R ^IV and R ^IV are each, independently from each other, hydrogen, C1-C10- alkyl, C6-Ci2-aryl, hetaryl with 5 to 10 atoms, wherein two adjacent radicals R ^1' , R ^11' , R ^111' , R ^IV , R ^v' , R ^vr , R ^vm' together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system with 1, 2 or 3 further rings, wherein the ring atoms are selected from carbon, oxygen and sulfur, and wherein each of the rings may carry 1, 2 or 3 substituents selected from halogen, CrC4-alkyl and C1-C4- alkoxy, wherein two radicals R ^IV and R ^v together with the carbon atoms of the benzene ring to which they are bound may also be a condensed ring system, wherein the ring atoms are selected from carbon, oxygen and sulfur, and wherein each of the rings may carry 1 , 2 or 3 substituents se lected from halogen CrC4-alkyl and CrC4-alkoxy. The ligand is selected in a manner, that a catalyst is formed, which has a low solubility in water. Preferably it is selected in way, that in the process step 3 the amount of ruthenium in the aque ous phase after the extraction is below 1 part per million. The below given ligands A-H will result in a ruthenium catalyst, which provides the required low solubility of the ruthenium catalyst in water.

In especially preferred embodiments, the ruthenium catalyst complex comprises at least one ligand selected from the formulae A to H and mixtures thereof

(S)-DM-SEGPHOS (S)-DTBM-SEGPHOS

D E

(Sj-MeO-BIPHEP (S)-DIFLUORPHOS (S)-C3-TUNEPHOS F G H

Abbreviations:

Me methyl Ph phenyl ‘Bu tert butyl

(S)-SEGPHOS (S)-(-)-5,5'-Bis(diphenylphosphino)-4,4'-bi-1,3-benzodioxole

(R)-BINAP (R)-(+)-(1,1 ‘-Binaphthalene-2, 2'-diyl)bis(diphenylphosphine)

(S)-SYNPHOS (S)-6,6'-Bis(diphenylphosphino)-2,2',3,3'-tetrahydro-5,5'- bibenzo[b][1 ,4]dioxine

(S)-DM-SEGPHOS (S)-(-)-5,5'-Bis(diphenylphosphino)-4,4'-bi-1,3-benzodioxole

(S)-DTBM-SEGPHOS (S)-(+)-5,5'-Bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosph ino]-4,4’-bi-

1,3-benzodioxole

(S)-MeO-BIPHEP (S)-(-)-2,2'-Bis(diphenylphosphino)-6,6'-di ethoxy-1,1 '-biphenyl

(S)-DIFLUORPHOS S-(+)-5,5'-Bis(diphenylphosphino)-2,2,2',2'-tetrafluoro-4,4' -bi-1,3- benzodioxole

(S)-C3-TUNEPHOS (S)-Bis(diphenylphosphino)-7,8-dihydro-6H-dibenzo[f,h][1 ,5]dioxonin

The ruthenium catalyst according to the invention can be employed in the form of a preformed complex, which comprises the ruthenium compound and one or more ligands. Alternatively, the ruthnium catalyst is formed in situ in the reaction medium by combining a metal compound, herein also termed pre-catalyst, with one or more suitable ligands to form a catalytically ruthenium complex in the reaction medium. It is also possible that the ruthenium catalyst is formed in situ in the presence of an auxiliary ligand by combining a metal compound, herein also termed pre-catalyst, with one or more auxiliary ligands to form a catalytically ruthenium complex in the reaction medium. Suitable pre-catalysts are selected from neutral ruthenium complexes, oxides and salts of ruthenium

Ruthenium compounds that are useful as pre-catalyst are, for example, [Ru(methylallyl)2COD], [Ru(p-cymene)Cl2]2, [Ru(benzene)Cl2]n, [Ru(CO)2Cl2]n, [Ru(CO) ₃ Cl2]2, [Ru(COD)(allyl)],

[RUCI ₃ H ₂ 0], [Ru(acetylacetonate) ₃ ], [Ru(DMSO) ₄ CI ₂ ], [Ru(PPh ₃ )3(CO)(H)CI], [Ru(PPh ₃ ) ₃ (CO)CI ₂ ], [Ru(PPh ₃ ) ₃ (CO)(H) ₂ ], [Ru(PPh ₃ ) ₃ CI ₂ ], [Ru(Cp)(PPh ₃ ) ₂ CI], [Ru(Cp) (CO) ₂ CI], [Ru(Cp)(CO) ₂ H], [Ru(Cp)(CO) ₂ ] ₂ , [Ru(Cp*)(CO) ₂ CI], [Ru(Cp*)(CO) ₂ H], [Ru(Cp*)(CO) ₂ ] ₂ , [Ru(indenyl)(CO)2CI], [Ru(indenyl)(CO)2H], [Ru(indenyl)(CO)2]2, ruthenocen, [Ru(binap)(CI)2], [Ru(2,2'-bipyridin) ₂ (CI) ₂ · H ₂ 0], [Ru(COD)(CI) ₂ H] ₂ , [Ru(Cp*)(COD)CI], [RU ₃ (CO)I ₂ ], [Ru(tetraphenylhydroxycyclopentadienyl)(CO)2H], [Ru(PMe ₃ )4(H)2], [Ru(PEt ₃ )4(H)2], [Ru(Pn- Pr ₃ )4(H) ₂ ], [Ru(Pn-Bu ₃ ) ₄ (H) ₂ ], [Ru(Pn-octyl ₃ ) ₄ (H) ₂ ], of which [Ru(methylallyl) ₂ COD],

RU(COD)CI ₂ ] ₂ , [Ru(Pn-Bu ₃ ) ₄ (H) ₂ ], [Ru(Pn-octyl ₃ ) ₄ (H) ₂ ], [Ru(PPh ₃ ) ₃ (CO)(H)CI] and [Ru(PPh ₃ ) ₃ (CO)(H)2] are preferred, in particular [Ru(methylallyl)2COD].

In the aforementioned compound, names "COD" denotes 1,5-cyclooctadiene; "Cp" denotes cyclopentadienyl; "Cp*" denotes pentamethylcycopentadienyl; and "binap" denotes 2,2'- bis(diphenylphosphino)-1 , 1 '-binaphthyl.

In the process of the invention, a sub-stoichiometric amount of the catalyst is generally used with the amount of catalyst typically being not more than 50 mol%, frequently not more than 20 mol% and in particular not more than 10 mol% or not more than 5 mol%, based on the amount of L-Sorbose in the L-Sorbose comprising composition. An amount of catalyst of from 0.001 to 50 mol%, frequently from 0.001 mol% to 20 mol% and in particular from 0.005 to 5 mol%, based on the amount of L-Sorbose in the L-Sorbose comprising composition, is gener ally used in the process of the invention. Preference is given to using an amount of catalyst of from 0.01 to 2 mol% and particularly preferably from 0.01 mol% to 1 mol%. All amounts of cata lysts indicated are calculated as ruthenium metal and based on the amount of L-Sorbose in the L-Sorbose comprising composition.

Typically, the amount of the chiral ligand present in the process of the invention is at least 0.5 mol, in particular at least 0.8 mol, especially at least 1 mol per 1 mol of ruthenium metal, e.g. in the range of 0.5 to 10 mol, in particular in the range of 0.8 to 8 mol and especially in the range from 1.0 to 5.0 mol per 1 mol of the transition metal.

The process of the invention can be carried out in the presence of a solvent. Suitable solvents are selected from aliphatic hydrocarbons, aromatic hydrocarbons, amides, ureas, nitriles, sul- foxides, sulfones, alcohols, esters, carbonates, ethers and mixtures thereof. Preferred solvents are aliphatic and alicyclic hydrocarbons, in particular those having 5 to 10 carbon atoms, such as pentane, hexane, heptane, octane, cyclohexane and methylcyclohexane; aromatic hydrocarbons including halogen containing aromatic hydrocarbons, such as benzene, toluene, xylenes, ethylbenzene, mesitylene or benzotrifluoride; amides, in particular N,N-dialkylamides of aliphatic carboxylic acids and N-alkyllactams, such as as dimethylformamide, diethylformamide, /V-methylpyrrolidone, N-ethylpyrrolidone or dimethylacetamide; ureas, in particular N,N,N’,N’-tetraalkyl ureas and N,N’-dialkyl-N,N’-alkylene ureas, such as tetramethylurea, N,N-dimethylimidazolinone (DMI) and N,N-dimethylpropyleneurea (DMPU); nitriles, in particular aliphatic nitriles, such as acetonitrile or propionitrile; sulfoxides, in particular dialkylsulfoxide, such as dimethyl sulfoxide; sulfones, in particular alicyclic sulfones, such as sulfolane; alcohols, in particular alkanols, such as methanol, ethanol, propanol, isopropanol, 1- butanol, iso-butanol, 1-propanol, iso-propanol, 1-hexanol; esters, in particular alkyl esters of aliphatic carboxylic acids, such as methyl acetate, ethyl acetate, f-butyl acetate and ethylbutyrate; carbonates, in particular dialkyl carbonates and alkylene carbonates, such as diethyl car bonate, ethylene carbonate and propylene carbonate; ethers, in particular dialkyl ethers and alicyclic ethers, such as dioxane, tetrahydrofurane, diethyl ether, dibutyl ether, methyl f-butyl ether, diisopropyl ether or diethylene glycol di methyl ether;

If desired, mixtures of two or more of the aforementioned solvents can also be used.

In a preferred embodiment, preferred solvent are alcohols, in particular CrCs-alkanols, such as methanol, ethanol, propanol, isopropanol, 1-butanol, iso-butanol, 1-propanol, iso-propanol, 1- hexanol or mixtures thereof.

Process step i)

The hydrogenation can principally be performed according to all processes known to a person skilled in the art, which are suitable for the hydrogenation of a L-Sorbose comprising composi tion. The hydrogen used for the hydrogenation can be used in pure form or, if desired, also in the form of mixtures with other, preferably inert gases, such as nitrogen or argon. Preference is given to using hydrogen in undiluted form.

The hydrogenation is typically carried out at a hydrogen pressure in the range from 0.1 to 300 bar, preferably in the range from 1 to 100 bar, more preferably in the range from 1 to 50 bar.

The hydrogenation is typically carried out at a temperature in the range from -20 to 300°C. The hydrogenation is preferably carried out at a temperature of at least 50°C, in particular at least 80°C. Preferably, the temperature will not exceed 200°C, in particular 180°C. The hydrogenation is in particular carried out at a temperature in the range of 50°C to 200°C and particularly preferably in the range from 80°C to 180°C. Temperatures of at most 150°C, e.g. in the range from 50 to 150°C, in particular in the range from 80 to 150°C, are particularly advantageous.

The hydrogenation can principally be performed in all reactors known by a person in the art for this type of reaction, and, therefore, will select the reactors accordingly. Suitable reactors are described for example in "Ullmanns Enzyklopadie der technischen Chemie", Vol. 1, 3rd edition, 1951, page 743 ff. Suitable pressure-resistant reactors are also known to a person skilled in the art and are described, for example, in "Ullmanns Enzyklopadie der technischen Chemie", Vol. 1, 3rd edition, 1951 , page 769 ff. Preferably, for the hydrogenation an autoclave is employed, which may have an internal stirrer and an internal lining.

In a preferred embodiment according to the invention, the obtained composition comprises L- Iditol as the main product and D-Sorbitol as the minor compound. The obtained composition is enriched in L-lditol and depleted in L-Sorbose, D-Mannitol and D-Sorbitol. The ratio of D- Sorbitol to L-lditol is in the range of 1:7 to 1 :1.5, preferably in the range of 1 :6.5 to 1:1.9. Be sides L-lditol and other hexitols, the reaction mixture also contains the solvent and the stereose lective ruthenium catalyst in the form of its resting state.

Process step ii)

From the reaction mixture obtained in step i), the L-lditol as the main product as well as the oth er hexoses were separated from the catalyst system. This separation is preferably performed as an extraction with water. The amount of water used is in a range of 3 to 100 mass equivalents according the L-lditol present in the residue obtained in step ii), preferably 5 to 15 mass equiva lents according the L-lditol present in the residue obtained in step ii). If a solvent was used in the hydrogenation reaction (step i)) providing a mixing gap with water, the L-lditol can be direct ly extracted from the reaction mixture. The extraction can be carried out in any state-of-the art extraction apparatus like mixer-settler. Another way to extract the products can be selective membranes, where only the hexitols can permeate and not the ruthenium catalyst. By this ex traction, the L-lditol as the main product and the other hexoses as minor products will be dis solved in the water, whereas the resting state of the ruthenium catalyst with a ligand as defined above will remain in the non-polar phase with a ruthenium concentration in the aqueous phase of not more than 1 ppm.

If the solvent used in step i) provides no mixing gap with water, like methanol, the products can also be extracted by first removing the solvent by distillation or in vacuo leaving a residue, from which the L-lditol as the main product as well as the other hexoses were extracted with water. This extraction can be performed in any setting used in the state of the art for extraction, like a stirred reactor, stirred tank, Soxhlet or filtration unit. In this step, the L-lditol as the main product and the other hexoses as minor products will be dissolved in the water, whereas the resting state of the ruthenium catalyst with a ligand as defined above will remain as insoluble solid with a ruthenium concentration in the aqueous phase of not more than 1 ppm. the remaining solid ruthenium catalyst in the form of its resting state is separated from the aqueous by any setting used in the state of the art for the separation of a liquid and solid like filtration, decanting or cen trifugation.

From the separated water phase, the L-lditol as the main product and the other hexoses as mi nor product can be obtained by evaporating of the water and used as obtained or further puri fied by state-of-the-art methods, if necessary.

Process step iii)

The separated catalyst in the form of its resting state obtained in step ii) is reactivated by adding a chloride source to the catalyst.

The chloride source can be HCI or a chloride salt or anion-exchange resins in a Cl-form. Preferred chloride salts are LiCI, NaCI, KCI, CaCh, MgCh, AlCh, FeCh. Preference is given to HCI as a methanolic solution or as HCI gas.

The amount of chloride used is in the range of 1 to 50 molar equivalent according the amount of ruthenium in the recycled catalyst, preferable in a range of 1 to 5 equivalents chloride according the ruthenium. After the reactivation of the catalyst according to step iii) the catalyst can be reused in the hy drogenation reaction (step i)), either immediately after step iii) or after a storage period. All process steps can either be run in a continuous- or in a discontinuous manner.

Without adding a chloride source, the activity and selectivity of the recycled catalyst is low (see comparative example).

The invention is described in more detail in the following examples.

EXAMPLES

All chemicals and solvents were purchased from Sigma-Aldrich, Merck or ABCR and were used without further purification.

Analytics of the reaction mixture after hydrogenation:

Samples of carbohydrates, e.g. hexoses, pentoses and, after a suitable hydrogenation, the cor responding sugar alcohols, were diluted in water to obtain a mass concentration of approxi mately 200 mg/ml prior to high-performance liquid chromatographic (HPLC) separation. Com positional analysis of the said samples was performed by the means of ion-moderated partition chromatography using refractive index detection. Known signals were quantified by external standard quantification. Separation was achieved using two serially coupled 300 mm x 7.8 mm Aminex HPX-87P columns (Bio-Rad Laboratories). Separation took place after injecting an ali quot of the sample into the HPLC system using deionized water as mobile phase at a column temperature of 80°C.

Example 1:

First Hydrogenation: In an argon-filled glovebox, a 180 mL Premex stainless steel autoclave fitted with a Teflon insert was charged with L-sorbose (7.35 g, 40.8 mmol), [RuCl2(benzene)]2 (0.109 g, 0.217 mmol), Ligand E (0.531 g, 0.450 mmol), MeOH (80 mL), and a stir bar. After the autoclave was closed, the reaction vessel was removed from the glovebox. The system was purged twice with hydrogen (20 bar) and then pressurized with hydrogen (60 bar, ca. 5 min) and placed into a preheated heating block (100 °C) over a magnetic stirring plate. While stirring overnight the pressure reached ca. 55 bar at the reaction temperature. After 12 h, the autoclave was then placed in a cold water bath, and after it was cooled to room temperature, it was de pressurized.

The golden-yellow solution was transferred to a round-bottom flask. The solution was evapo rated and dried in vacuo to yield a yellow-brown sticky residue. The rest of the residue was mixed with distilled water (50 ml_) and the light brown suspension was filtered over a fritted filter (0 3.5 cm, pore size 4) and then over a pad of celite (0 3.5 cm, 7-10 mm high) sitting on a fritted filter (0 3.5 cm, pore size 4). A sample (1 ml_) of the lime-like colored solution was submitted to ICP-MS analysis. The ruthenium-content in this solution was 1 mg/kg as determined by ICP/MS.

The brown filter cake was washed with distilled water (2 x 10 ml_) and dried in vacuo to yield 537.7 mg of the ruthenium catalyst in its resting state. These two combined aqueous fractions were filtered over a pad of celite (0 3.5 cm, 7-10 mm high) sitting on a fritted filter (03.5 cm, pore size 4) and added to the above-mentioned aqueous fraction. The solution was dried using the cryovap method ( OPRD 2020, 24, 25) followed by drying on the high vacuum over the weekend resulting in a highly viscous lime-colored liquid (7.80 g). According HPLC analysis of this viscous lime-colored liquid, the conversion of L-Sorbose was 99% and the overall selectivity towards L-lditol and D-Sorbitol was 98%. The ratio between L-lditol to D-Sorbitol was 6.7 to 1, according a L-lditol yield of 84.4 % after the first hydrogenation.

Second Hydrogenation with recycled catalyst and HCI addition:

In an argon-filled glovebox, a 60 mL Premex stainless steel autoclave fitted with a Teflon insert was charged with L-Sorbose (730 mg, 4.05 mmol), the catalyst obtained after the product ex traction from the first hydrogenation (62 mg), MeOH (8 mL), 0.5 M methanolic HCI (0.16 mL, 0.08mmol), and a stir bar. After it was closed, the reaction vessel was removed from the glove- box and placed into a preheated heating block (100 °C) over a magnetic stirring plate. After 16h, the autoclave was then placed in a cold water bath, and after it was cooled to room tempera ture, it was depressurized.

The volatiles of a sample (2 mL) of the brown solution were evaporated to dryness. The residue was dissolved in distilled water (2 mL). The suspension was filtered over a pad of celite and subsequently through a PTFE syringe filter (0.2 pm) and submitted to HPLC analysis. According HPLC, the conversion of L-Sorbose was 98% and the overall selectivity towards L-lditol and D- Sorbitol was 96%. The ratio between L-lditol to D-Sorbitol was 6.4 to 1, according a L-lditol yield of 84.4 % after the first hydrogenation.

Comparative Example 1:

Second Hydrogenation with recycled catalyst but without HCI addition:

In an argon-filled glovebox, a 60 mL Premex stainless steel autoclave fitted with a Teflon insert was charged with L-Sorbose (736.2 mg, 4.09 mmol), the catalyst after the product extraction from the first hydrogenation of example 1 (74.0 mg), MeOH (8 mL), and a stir bar (15:05). After it was closed, the reaction vessel was removed from the glovebox and placed into a preheated heating block (100 °C) over a magnetic stirring plate. After 16 h, the autoclave was then placed in a cold water bath, and after it was cooled to room temperature, it was depressurized.

The solvent of the yellow-brown solution was evaporated and the brown residue was dissolved in dest. water (8 ml_). The light brown suspension was subjected to centrifugation (40,000 rpm, 30 min). The supernatant was filtered through a PTFE syringe filter (0.2 pm) and submitted to HPLC analysis. According HPLC, the conversion of L-Sorbose was 88% and the overall selec tivity towards L-lditol and D-Sorbitol was 91%. The ratio between L-lditol to D-Sorbitol was 1.8 to 1 , according a L-lditol yield of 51.5 % after the first hydrogenation. This comparative experi- ment shows, that without adding a chloride source, the activity and selectivity significantly drops when the catalyst is recycled.