DE102006032499B4 - Process for the preparation of enantiomerically pure flavanones - Google Patents

Abstract

wobei R¹ und R² ausgewählt sind aus H, Alkyl und Halogen,
wobei R³ und R⁵ ausgewählt sind aus Alkyl und Acyl,
wobei R⁴ ausgewählt ist aus H, Alkyl und Acyl,
wobei Alkyl jeweils ausgewählt ist aus unsubstituierten oder substituierten, gesättigten oder ungesättigten, geradkettigen oder verzweigten Alkylgruppen mit 1 bis 15 Kohlenstoffatomen und Acyl jeweils ausgewählt ist aus unsubstituierten oder substituierten, gesättigten oder ungesättigten, geradkettigen oder verzweigten Acylgruppen mit 1 bis 10 Kohlenstoffatomen,
mit einem Gemisch aus Ameisensäure und einer Base,
in Gegenwart eines chiralen Katalysators der allgemeinen Formel:

enthaltend:
– ein Zentralmetall M ausgewählt aus Rhodium (III), Ruthenium (II) oder Iridium (III),
– einen π-Liganden A der allgemeinen Formel:

wobei R⁵ und R⁶ ausgewählt sind aus Alkyl und unsubstituiertem oder substituiertem...Process for the preparation of a (2S) - or (2R) -flavanone with the steps:
a) Reduction of a racemic mixture of a flavanone of the general formula rac-1:

wherein R ¹ and R ^{2 are} selected from H, alkyl and halogen,
wherein R ³ and R ^{5 are} selected from alkyl and acyl,
wherein R ^{4 is} selected from H, alkyl and acyl,
wherein each alkyl is selected from unsubstituted or substituted, saturated or unsaturated, straight-chain or branched alkyl groups having 1 to 15 carbon atoms and acyl is in each case selected from unsubstituted or substituted, saturated or unsaturated, straight-chain or branched acyl groups having 1 to 10 carbon atoms,
with a mixture of formic acid and a base,
in the presence of a chiral catalyst of the general formula:

including:
A central metal M selected from rhodium (III), ruthenium (II) or iridium (III),
A π-ligand A of the general formula:

wherein R ⁵ and R ^{6 are} selected from alkyl and unsubstituted or substituted ...

Description

The The invention relates to a process for the preparation of enantiomerically pure Flavanones, in particular prenylated flavanones. Such flavanones are characterized by diverse useful bioactivity from (review article: "Prenylated flavonoids: pharmacology and biotechnology ", Botta, B .; Vitali, A .; Menendez, P .; Misiti, D .; Delle Monache, G. Curr. Med. Chem. 2005, 12, 713-739) and are in the field of Pharmacy and cosmetics applicable.

A Variety of flavanones can be isolated from plants (Harborne, J. B .; Baxtor, H. (ed.) The Handbook of Natural Flavonoids, Vol. 1 + 2, Wiley: New York, 1999), where in principle only the naturally occurring Enantiomer available and the yield is often very low.

The chemical synthesis of flavanones has so far led to a 1: 1 mixture the enantiomers (review article: "Stereoselective synthesis of monomeric flavonoids ", Marais, J.P.J .; Ferreira, D .; Slade, D. Phytochemistry 2005, 66, 2145-2176).

Flavanone enantiomers were previously by separation of the racemic mixture by HPLC obtained at chiral phases. This method was z. B. for as SERM (= selective estrogen receptor modulator) active compound 8-prenylnaringenin both on an analytical scale ("Prenylflavonoids: A new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship ", Kitaoka, M., Kadokawa, H.; Sugano, M .; Ichikawa, K .; Taki, M .; Takaishi, S .; Iijima, Y .; Tsutsumi, S .; Boriboon, M .; Akiyama, T. Planta Med. 1998, 64, 511-515), as also on a preparative scale ("tissue specificity of 8-prenylnaringenin: Protection from ovariectomy induced bone loss with minimal trophic effects on the uterus ", Hümpel, M .; Isaksson, P .; Schaefer, O .; Kaufmann, U .; Ciana, P .; Maggi, A .; Schleuning, W. -D. J. Steroid Biochem. Mol. Biol. 2005, 97, 299-305) carried out.

For different Flavanoids have also been described as biotechnological processes with those of course occurring (2S) -configured enantiomers are selectively accessible ("Efficient production of (2S) flavanones by Escherichia coli containing artificial biosynthetic gene cluster ", Miyahisa, I., Kaneko, M .; Funa, N., Kawasaki, H.; Kojima, H .; Ohnishi, Y .; Horinouchi, S. Appl. Microbiol. Biotechnol. 2005 68, 498-504; "Biosynthesis of natural flavanones in Saccharomyces cerevisiae ", Yan, Y. Kohli, A., Koffas, M.A. G. Appl. Environ. Microbiol. 2005, 71, 5610-5613; "Flavanone 8-dimethylallyltransferase in Sophora flavescens cell suspension cultures ", H. Yamamoto, M. Senda, K. Inoue, Phytochemistry 2000, 54, 649-655).

The Use of HPLC on chiral phases is due to the high price these materials especially for enantiomeric separations in preparative scale extremely expensive. Biotechnological processes are so far only for few flavanones have been studied. At the moment it is still unclear, if one preparative presentation pure flavanone enantiomers will be possible in this way. A general usable method is not in sight here, and even the pharmaceutical Industry is currently taking over a separation of flavanone enantiomers, z. B. of 8-prenylnaringenin, by HPLC on chiral phases. In addition, by participating in the flavanone biosynthesis involved Enzymes as well as by the direct isolation of flavanones from natural Only the (2S) -enantiomers are accessible in pure form.

It It is therefore an object of the invention to provide a method the efficient production of pure (2S) and (2R) enantiomers allowed by flavones.

mit
R¹ = H, Alkyl oder Halogen
R² = H, Alkyl oder Halogen
R³ = Alkyl oder Acyl
R⁴ = H, Alkyl oder Acyl
R⁵ = Alkyl oder Acyl
mit einem Gemisch aus Ameisensäure und einer Base, vorzugsweise einem tertiären Amin, besonders bevorzugt Triethylamin, in Gegenwart eines chiralen Katalysators selektiv reduziert wird.According to the invention the object is achieved by a process in which a racemic mixture of a flavanone of the general formula rac-1:

With
R ¹ = H, alkyl or halogen
R ² = H, alkyl or halogen
R ³ = alkyl or acyl
R ⁴ = H, alkyl or acyl
R ⁵ = alkyl or acyl
is selectively reduced with a mixture of formic acid and a base, preferably a tertiary amine, more preferably triethylamine, in the presence of a chiral catalyst.

enthaltend:

• – ein Zentralmetall M ausgewählt aus Rhodium (III), Ruthenium (II) oder Iridium (III),
• – einen π-Liganden A der allgemeinen Formel:
  
  wobei R⁵ und R⁶ ausgewählt sind aus Alkyl und Aryl, wobei R⁷ und R⁸ ausgewählt sind aus H und Alkyl,
• – einen chiralen Diamin-Liganden der allgemeinen Formel:
  
  wobei R¹, R² und R³ ausgewählt sind aus Aryl und Alkyl, wobei R⁴ ausgewählt ist aus H und Alkyl, wobei gegebenenfalls der chirale Diamin-Ligand und der π-Ligand A kovalent über deren Substituenten
• – R³ und R⁵ oder
• – R⁴ und R⁵ oder
• – R³ und R⁶ oder
• – R⁴ und R⁶ verbrückt sein können.
• – einen Liganden B, der in der katalytisch aktiven Spezies Wasserstoff bedeutet (B = H).

The chiral catalyst is a metal complex of the general formula:

including:

• A central metal M selected from rhodium (III), ruthenium (II) or iridium (III),
• A π-ligand A of the general formula:
  
  wherein R ⁵ and R ^{6 are} selected from alkyl and aryl, wherein R ⁷ and R ^{8 are} selected from H and alkyl,
• A chiral diamine ligand of the general formula:
  
  wherein R ¹ , R ² and R ^{3 are} selected from aryl and alkyl, wherein R ^{4 is} selected from H and alkyl, optionally wherein the chiral diamine ligand and the π-ligand A covalently via their substituents
• - R ³ and R ⁵ or
• - R ⁴ and R ⁵ or
• - R ³ and R ⁶ or
• - R ⁴ and R ⁶ can be bridged.
• A ligand B which in the catalytically active species is hydrogen (B = H).

For the reaction may also be the chloride or other derivative of the chiral catalyst with respect to the ligand B (B = Cl or another suitable Anion) are used, since this under the reaction conditions is immediately converted into the catalytically active metal hydride (B = H).

By the inventive method Advantageously, only one enantiomer is highly selectively transfer hydrogenated.

If an (R, R) -diamine ligand is used, the (2R) -enantiomer of flavanone 1 is hydrogenated, where R ⁴ ≠ acyl is the alcohol having the general formula (2R, 4R) -2. The mixture is obtained as:

If an (S, S) -diamine ligand is used, the (2S) -enantiomer of flavanone 1 is hydrogenated, where R ⁴ ≠ acyl is the alcohol having the general formula (2S, 4S) -2. The mixture is obtained as:

Advantageous let yourself the unreacted enantiomer 1 is very simply from the reaction product separate. Preferably, this separation is done at ordinary Silica gel, preferably in a column chromatography.

The Transfer hydrogenation according to the invention shows a surprising high enantioselectivity - over 95% ee (enantiomeric excess) - for different substituted flavanones, whereby this method by a size Application width distinguishes.

moreover is the enantioselectivity the transfer hydrogenation according to the invention much stronger pronounced as in the few known examples of the kinetic resolution of β-chiral ketones with other methods ("Asymmetric Hydrogenation of cyclic α, β-unsaturated ketones to chiral allylic alcohols ", Ohkuma, T .; Ikehira, H .; Ikariya, T .; Noyori, R. Synlett 1997, 467-468; "An efficient enantioselective synthesis of (+) - (R, Z) -5-muscenone and (-) - (R) -muscone - An example of a kinetic resolution and enantioconvergent transformation ", Fehr, C .; Galindo, J .; Etter, O. Eur. J. Org. Chem. 2004, 1953-1957). The transfer hydrogenation according to the invention is easy to use. A control of sales while the reaction is not necessary since this completely stops after hydrogenation of one enantiomer.

Not Completely racemic starting material 1 can also according to this method simply continue to be enantiomerically enriched.

In the radicals R ¹ , R ² , R ³ , R ⁴ and R ^{5 of} the general formula of the flavanone rac-1, alkyl represents an unsubstituted or substituted, saturated or unsaturated, straight-chain or branched alkyl group having 1 to 15 carbon atoms preferably selected from CH ₃ , C ₂ H ₅ , C ₂ H ₃ , C ₃ H ₇ , C ₃ H ₅ , C ₄ H ₉ , C ₄ H ₇ , C ₅ H ₁₁ , C ₅ H ₉ , C ₁₀ H ₂₁ , C ₁₀ H ₁₇ , C ₁₅ H ₃₁ and C ₁₅ H ₂₅ , particularly preferably selected from methyl, ethyl, ethenyl (vinyl), n-propyl, isopropyl, 2-propenyl (allyl), n-butyl, isobutyl, Butyl, 1-methylpropyl, tertiary-butyl, 3-methylbutyl, 1,1-dimethylpropyl, 3-methyl-2-butenyl (prenyl), 1,1-dimethylallyl, geranyl and farnesyl, as well as diastereomers and hydrogenated derivatives of geranyl and farnesyl, such as B. the hydrogenated residues 3,7-dimethyloctyl and 3,7,11-trimethyldodecyl.

In the radicals R ³ , R ⁴ and R ^{5 of} the general formula of the flavanone rac-1, acyl is an unsubstituted or substituted, saturated or unsaturated, straight-chain or branched acyl group having 1 to 10 carbon atoms, particularly preferably 1 to 5 carbon atoms Acyl group is preferably selected from C _n H _{2n + 1} -CO with n = 0 to 4, particularly preferred is acetyl with n = 1.

In the radicals R ¹ and R ^{2 of} the general formula of flavanone 1, halogen is selected from iodine, bromine, chlorine and fluorine.

In the π-ligand A, alkyl in R ⁵ , R ⁶ , R ⁷ and R ^{8 represents} an unsubstituted or substituted, saturated or unsaturated, straight-chain or branched alkyl group having a chain length of 1 to 4 carbon atoms. Alkyl is preferably in R ⁵ , R ⁶ , R ⁷ and R ^{8 are} selected from methyl, ethyl, n-propyl or iso-propyl.

In the π-ligand A, aryl in R ⁵ and R ^{6 represents} an unsubstituted or substituted phenyl group preferably having 6 to 8 carbon atoms.

The π ligand A is preferably selected from pentamethylcyclopentadienyl (Cp *), 1-methyl-4-isopropylbenzene or 1,3,5-trimethylbenzene.

In the chiral diamine ligand, alkyl in R ¹ , R ² , R ³ and R ^{4 represents} an unsubstituted or substituted, saturated or unsaturated, straight-chain or branched alkyl group having a chain length of 1 to 4 carbon atoms. More preferably, the radicals R ¹ and R ² in the chiral diamine ligand is covalently linked to an unsubstituted or substituted 3- to 5-membered chain, more preferably to (CH ₂ ) ₄ .

In the chiral diamine ligand, aryl in R ¹ , R ² and R ^{3 represents} an unsubstituted or substituted phenyl Aryl in R ¹ , R ² and R ³ in the chiral diamine ligand is preferably selected from phenyl or p-tolyl.

The chiral diamine, which forms the diamine ligand in the catalyst preferably selected from (R, R) -N-p-tolylsulfonyl-1,2-diphenylethylenediamine, (S, S) -N-p-tolylsulfonyl-1,2-diphenylethylenediamine, (R, R) -N-p-tolylsulfonyl-1,2-cyclohexanediamine or (S, S) -N-p-tolylsulfonyl-1,2-cyclohexanediamine.

The π ligand A and the chiral diamine ligand may be covalently linked together. The radicals R ³ and R ⁵ , or the radicals R ⁴ and R ⁵ , or the radicals R ³ and R ⁶ , or the radicals R ⁴ and R ^{6 are} preferably covalently to an unsubstituted or substituted 2- to 4-membered chain connected. Particularly preferred is a covalent linkage of the radicals R ⁴ and R ⁵ , or the radicals R ⁴ and R ⁶ to a 3-membered carbon chain.

Preferably a catalyst with rhodium (III) is used as the central metal. Advantageously, the chiral rhodium catalyst in a load of preferably up to 2 mol% based on the flavanone used.

One Mixture of formic acid and a base, preferably a tertiary amine, particularly preferred Triethylamine, serves advantageously as a reducing agent. Especially preferred reducing agents are formic acid / triethylamine and sodium formate.

mit Ph = Phenyl und Ts = p-TolylsulfonylThe chiral rhodium catalyst 3 is preferably used, which consists of pentamethylcyclopentadienylrhodium chloride dimer - [Cp * RhCl ₂ ] ₂ - and the chiral diamine (R, R) - or (S, S) -N-p-tolylsulfonyl-1,2-diphenylethylenediamine - (R, R) - or (S, S) -tsdpen - is formed in the presence of formic acid and triethylamine.

with Ph = phenyl and Ts = p-tolylsulfonyl

This Reagent system has hitherto been used for enantioselective reduction prochiral ketones ("rhodium versus ruthenium: contrasting behavior in the asymmetric transfer hydrogenation of α-substituted acetophenones " Cross, D.J .; Kenny, J.A .; Houson, I .; Campbell, L .; Walsgrove, T .; Wills, M. Tetrahedron: Asymmetry 2001, 12, 1801-1806; "Practical synthesis of optically active styrene oxides via reductive transformation of 2-chloroacetophenones with chiral rhodium catalysts ", Hamada, T .; Toni, T .; Izawa, K .; Noyori, R .; Ikariya, T. Org. Lett. 2002, 4, 4373-4376).

By Utilization of the (R, R) and the (S, S) enantiomers The diamine may optionally contain the (2S) or (2R) enantiomer of flavanone 1 are obtained. An advantage is an insulation the chiral rhodium catalyst 3 or its first formed Pre-stage (3 with Rh-Cl instead of Rh-H) not required.

The appropriate application of modified catalyst systems, for. B. by changing the central metal atom from rhodium (III) to ruthenium (II) or iridium (III), by exchange of the π ligand without change the total electron number, such as a change of pentamethylcyclopentadienyl to 1-methyl-4-isopropylbenzene or 1,3,5-trimethylbenzene, or by variation of the chiral diamine ligand corresponds to that to be protected Method.

Of the Product alcohol (2R, 4R) -2 or (2S, 4S) -2 may advantageously after separation of unreacted isomer (2S) -1 or (2R) -1 by oxidation in the other enantiomer of 1 is converted.

This is preferably carried out with catalytic amounts of tetrapropylammonium peruthenate (TPAP) and N-methylmorpholine N-oxide (NMO) as a co-oxidant. It will be preferably 5 mol% TPAP and 2 molar equivalents NMO used.

The reaction equation of the oxidation is given as an example for the (2R) -isomer:

Advantageous can be achieved by the enantioselective transfer hydrogenation and the subsequent Oxidation of the reduction product as a result both flavanone enantiomers obtained in high yield.

embodiments

Based following embodiments the invention will be closer explained.

a) Enantioselective transfer hydrogenation

rac-1 R¹ R² R³ R⁴ R⁵ Mol-% (R,R)-3 (2S)-1 (2R,4R)-2 Ausbeute (%)^a ee (%)^b Ausbeute (%)^a ee (%) a Prenyl H Ac H Ac 2 43 > 99 41 > 95^c b Prenyl H Ac Ac Ac 2 47 > 99 - c Prenyl H Ac Me Ac 2 25 > 99 15 n. b.^d d H 1,1-Dimethylallyl Ac H Ac 2 48 > 99 47 > 95^c e H H Ac H Ac 2 30 > 99 25 n. b.^d f H H Ac Ac Ac 2 45 n. b.^d - g Me H Me Me Me 10 49 > 99 48 > 95^c h Br H Me Me Me 20 54 85 46 > 99^b

• ^a Isolierte Ausbeute. ^b ee = Enantiomerenreinheit. Mittels chiraler HPLC bestimmt. (2S)-1a und (2S)-1b: Daicel AD, Hexan/Isopropanol 8:2; (2S)-1c: Daicel OD, Hexan/Isopropanol 8:2; (2S)-1d: Daicel AD, Hexan/Isopropanol 95:5; (2S)-1e: Daicel AD, Hexan/Isopropanol 9:1; (2S)-1g: Daicel OD, Hexan/Isopropanol 7:3; (2S)-1h und (2R,4R)-2h: Daicel OD, Hexan/Isopropanol 1:1. ^c Nach Oxidation zu (2R)-1 mittels Drehwertmessung bestimmt. ^d Nicht bestimmt. Ac = Acetyl, Me = Methyl, Prenyl = 3-Methyl-2-butenyl.

The following table illustrates some applications using the example of enantioselective reduction of the enantiomer (2R) -1 using the catalyst (R, R) -3 with rhodium (III) as the central metal, pentamethylcyclopentadienyl (Cp *) as the π ligand, and (R , R) -enantiomers of the chiral diamine tsdpen (Np-tolylsulfonyl-1,2-diphenylethylenediamine):

rac-1 R ¹ R ² R ³ R ⁴ R ⁵ Mol% (R, R) -3 (2S) -1 (2R, 4R) -2 Yield (%) ^a ee (%) ^b Yield (%) ^a ee (%) a prenyl H Ac H Ac 2 43 > 99 41 > 95 ^c b prenyl H Ac Ac Ac 2 47 > 99 - c prenyl H Ac me Ac 2 25 > 99 15 nb ^d d H 1,1-dimethylallyl Ac H Ac 2 48 > 99 47 > 95 ^c e H H Ac H Ac 2 30 > 99 25 nb ^d f H H Ac Ac Ac 2 45 nb ^d - G me H me me me 10 49 > 99 48 > 95 ^c H br H me me me 20 54 85 46 > 99 ^b

• ^a Isolated yield. ^b ee = enantiomeric purity. Determined by chiral HPLC. (2S) -1a and (2S) -1b: Daicel AD, hexane / isopropanol 8: 2; (2S) -1c: Daicel OD, hexane / isopropanol 8: 2; (2S) -1d: Daicel AD, hexane / isopropanol 95: 5; (2S) -1e: Daicel AD, hexane / isopropanol 9: 1; (2S) -1g: Daicel OD, hexane / isopropanol 7: 3; (2S) -1h and (2R, 4R) -2h: Daicel OD, hexane / isopropanol 1: 1. ^c After oxidation to (2R) -1 determined by means of a rotation value measurement. ^d Not determined. Ac = acetyl, Me = methyl, prenyl = 3-methyl-2-butenyl.

Method for producing enantiomerically pure flavanones by kinetic resolution on the example of the compounds (2S) -1a, ce (R ¹ -R ⁵ see Table):

To a 0.08 molar solution of the racemic flavanone rac-1 in ethyl acetate is added a solution of the catalyst (R, R) -3 obtained by addition of [Cp * RhCl ₂ ] ₂ (1 mol%) and (R, R) -tsdpen (2 mol%) in ethyl acetate (6.7 mL / 0.1 mmol [Cp * RhCl ₂ ] ₂ ) with a 3.6: 1 (v / v) mixture of NEt ₃ / HCO ₂ H (2.7 mL / 0.1 mmol [Cp * RhCl ₂ ] ₂ ) and vortexed for 30 min at room temperature. The reaction mixture is stirred for 2 h at room temperature and treated with saturated NaHCO ₃ solution. After phase separation, the organic phase is washed once more with saturated NaHCO ₃ solution, dried over MgSO ₄ , and the solvent removed in vacuo. The unreacted enantiomer (2S) -1 is separated from the reaction product (2R, 4R) -2 by column chromatography on silica gel. For this purpose, the silica gel is deactivated with 1% NEt ₃ in pentane / ethyl acetate 1: 1 (v / v), the ketone (2S) -1 is eluted with pentane / ethyl acetate 1: 1 (v / v) and then the alcohol (2R, 4R) -2 is rapidly rinsed from the column with ethyl acetate.

distance of the solvent in vacuo, the pure products provide (2S) -1 and (2R, 4R) -2.

b) oxidation of the alcohol 2

(2R,4R)-2 R¹ R² R³ R⁴ R⁵ Ausbeute (2R-1) (%)^a ee (2R-1) (%)^b a Prenyl H Ac H Ac 64 > 95 d H 1,1-Dimethylallyl Ac H Ac 89 > 95 g Me H Me Me Me 99 > 95

• ^a Isolierte Ausbeute. ^b Mittels Drehwertmessung bestimmt. Ac = Acetyl, Me = Methyl, Prenyl = 3-Methyl-2-butenyl.

After separation of the unreacted enantiomer (2S) -1, the alcohol (2R, 4R) -2 can be oxidized to flavanone (2R) -1. The following table illustrates some applications:

(2R, 4R) -2 R ¹ R ² R ³ R ⁴ R ⁵ Yield (2R-1) (%) ^a ee (2R-1) (%) ^b a prenyl H Ac H Ac 64 > 95 d H 1,1-dimethylallyl Ac H Ac 89 > 95 G me H me me me 99 > 95

• ^a Isolated yield. ^b Determined by means of a rotation value measurement. Ac = acetyl, Me = methyl, prenyl = 3-methyl-2-butenyl.

A 0.02 molar solution of the corresponding alcohol (2R, 4R) -2 (R ¹ -R ⁵ see Table) in dry CH ₂ Cl ₂ is dissolved under argon with molecular sieve 4A and 2 molar equivalents of N-methylmorpholine-N-oxide (NMO). added and stirred for 15 min at room temperature. After addition of 5 mol% of tetrapropylammonium perruthenate (TPAP) stirring is continued at room temperature until the reaction is complete (about 30 min, TLC). The mixture is then filtered through a silica gel frit with ethyl acetate and the product is purified by column chromatography on silica gel (elution with pentane / ethyl acetate 1: 1 v / v). Removal of the solvent in vacuo gives the pure product (2R) -1.

Claims (12)

A process for preparing a (2S) - or (2R) -flavanone comprising the steps of: a) reducing a racemic mixture of a flavanone of the general formula rac-1:

wherein R ¹ and R ^{2 are} selected from H, alkyl and halo, wherein R ³ and R ^{5 are} selected from alkyl and acyl, wherein R ^{4 is} selected from H, alkyl and acyl, wherein each alkyl is selected from unsubstituted or substituted, saturated or unsaturated, straight-chain or branched alkyl groups having 1 to 15 carbon atoms and acyl is in each case selected from unsubstituted or substituted, saturated or unsaturated, straight-chain or branched acyl groups having 1 to 10 carbon atoms, with a mixture of formic acid and a base, in the presence of a chiral Catalyst of the general formula:

comprising: a central metal M selected from rhodium (III), ruthenium (II) or iridium (III), a π-ligand A of the general formula:

wherein R ⁵ and R ^{6 are} selected from alkyl and unsubstituted or substituted phenyl, wherein R ⁷ and R ^{8 are} selected from H and alkyl, - a chiral diamine ligand of the general formula:

wherein R ¹ , R ² and R ^{3 are} selected from alkyl and unsubstituted or substituted phenyl, wherein R ^{4 is} selected from H and alkyl, wherein in the π-ligand A and in the chiral diamine ligand alkyl is in each case selected from unsubstituted or substituted, saturated or unsaturated, straight-chain or branched alkyl groups having a chain length of 1 to 4 carbon atoms - a ligand B selected from H, chloride or another suitable anion, wherein when an (R, R) -diamine ligand is used, only the (2R) -enantiomer of flavanone 1 is hydrogenated, and when an (S, S) -diamine ligand is used, only the (2S) -enantiomer of flavanone 1 is hydrogenated; b) separating the unreacted enantiomer (2S) -1 or (2R) -1 from the respective reduced product. Process according to Claim 1, characterized in that the following substance mixtures are present as the result of step a):

Process according to Claim 1 or 2, characterized in that the alkyl in at least one of the radicals R ¹ , R ² , R ³ , R ⁴ and / or R ⁵ in the general formula rac-1 is selected from CH ₃ , C ₂ H ₅ , C ₂ H ₃ , C ₃ H ₇ , C ₃ H ₅ , C ₄ H ₉ , C ₄ H ₇ , C ₅ H ₁₁ , C ₅ H ₉ , C ₁₀ H ₂₁ , C ₁₀ H ₁₇ , C ₁₅ H ₃₁ and C ₁₅ H ₂₅ . Method according to one of claims 1 to 3, characterized in that the halogen in at least one of the radicals R ¹ and / or R ² in the general formula rac-1 is selected from iodine, bromine, chlorine and fluorine. Method according to one of claims 1 to 4, characterized in that the acyl in at least one of R ³ , R ⁴ and / or R ⁵ in the general formula rac-1 is selected from C _n H _{2n + 1} -CO with n = 0 to 4. Method according to one of claims 1 to 5, characterized that the π ligand A is selected from pentamethylcyclopentadienyl (Cp *), 1-methyl-4-isopropylbenzene or 1,3,5-trimethylbenzene. Method according to one of claims 1 to 6, characterized that the chiral diamine, that in the catalyst the diamine ligand forms, selected is (R, R) -N-p-tolylsulfonyl-1,2-diphenylethylenediamine, (S, S) -N-p-Tolylsulfonyl-1,2-diphenylethylenediamine, (R, R) -N-p-tolylsulfonyl-1,2-cyclohexanediamine or (S, S) -Np-tolylsulfonyl-1,2-cyclohexanediamine. Method according to one of claims 1 to 5, characterized in that the chiral diamine ligand and the π-ligand A via the substituents R ³ or R ^{4 of} the diamine ligand and the substituents R ⁵ or R ^{6 of} the π-ligand A covalently connected to each other. Method according to one of claims 1 to 8, characterized that as a reducing agent, a mixture of formic acid with a tertiary Amine, preferably triethylamine, or sodium formate used becomes. Method according to one of claims 1 to 9, characterized that separating the unreacted enantiomer with silica gel he follows. Method according to one of claims 1 to 10, characterized that the reduced product is subsequently oxidized. Method according to claim 11, characterized in that that oxidation with tetrapropylammonium perruthenate (TPAP) and N-methylmorpholine-N-oxide (NMO) takes place.