The way enantioselective obtain optically active substituted derivatives of 5,6-dihydro-2h-piran-2-it

 

(57) Abstract:

The invention relates to a new catalytic method for obtaining optically active compounds of General formula (I),

< / BR>
where R1and R2denote alkyl, which can be broken by oxygen atom in a different position than the position, or optionally substituted benzyl;

R3denotes hydrogen, lower alkyl, optionally substituted benzyl, -CO R4, -COOR4or-CONR24;

R4denotes lower alkyl or aryl,

asymmetric hydrogenation of compounds of formula (II)

< / BR>
where R1, R2, R3have the above values,

asimetricna hydronaut in the presence of a complex of optically active, preferably atropoisomeric of lifestyleand with the metal of group VIII. The task is to find direct access to optically active compounds of formula (I), which is unnecessary subsequent splitting of the racemate. 6 C.p. f-crystals, 2 tab.

The invention relates to a new catalytic method for obtaining optically active compounds of General formula I

< / BR>
where R1and R2denote alkyl, which can be broken will teachet hydrogen, lower alkyl, optionally substituted benzyl, -CO-R4, -COOR4or-CONR24and

R4denotes lower alkyl or aryl.

The compounds of formula 1 are known compounds and are valuable intermediate products for pharmacologically applicable final products. They can be converted, as described in European patent 443449, and used in pharmaceuticals for inhibition of pancreatic lipase. Patent EP 443449 is the closest analogue of the claimed invention.

The present invention is to find direct access to optically active compounds of the formula I, which is unnecessary subsequent splitting of the racemate.

The problem is solved in that the compound of General formula II

< / BR>
where R1, R2, R3have the above values, asymmetrically hydronaut in the presence of a complex of optically active atropoisomeric diphosphine-ligand with the metal of group VIII.

As the optically active complex metal-diphosphine for proposed invention of the method are discussed, in particular, optically active complexes of ruthenium General formulas
>/BR>RuL(X4)2III-d

where X1denotes BF-4, ClO-4, B(phenyl)-4, SbF-6PF-6, Z1-SO-3,

X1denotes halogen,

X2denotes benzene, hexamethylbenzene or para-timol,

X3denotes a halide, ClO-4, B(phenyl)-4, SbF-6PF-6, Z1-SO-3or BF-4,

X4denotes the anion Z2-COO-or the anion Z3-SO-3,

Z1denotes a halogenated lower alkyl or halogenated lower phenyl,

Z2denotes lower alkyl, phenyl, halogenated lower alkyl or halogenated phenyl,

Z3denotes lower alkyl or phenyl,

L represents an optically active, atropoisomeric diphosphine-ligands of the formula IV

< / BR>
or the General formula V

< / BR>
in (S)- or (R)- form, where R5and R6independently of one another represent lower alkyl, lower alkoxy, di(lower alkyl) amino, hydroxyl group, protected hydroxyl group, hydroxymethyl or a protected hydroxymethyl, or R5and R6together represent the divalent gr alkyl or lower alkoxy,

R8and R9independently of one another denote cyclo-alkyl, unsubstituted or substituted phenyl or five-membered heteroaromatic hydrocarbon, with the proviso that at least one of the radicals R8and R9represents a substituted phenyl ring or five-membered heteroaromatic hydrocarbon,

R10represents preferably in position 5,5' halogen, hydroxyl group, lower alkyl, amino, acetamido, nitro or sulfo, R11denotes lower alkyl, phenyl or benzyl,

R12denotes lower alkyl, or both R12are together di - or trimethylene,

p represents zero or the integer 1, 2 or 3, and

q denotes a number of 3, 4 or 5.

In accordance with the compounds of formulas 1-V, the following definitions General expressions have a meaning regardless of whether there are data expression independently or in combination.

The expression "alkyl, which can be broken by oxygen atom in a different situation than or position" means in the framework of this application alkyl group with 1 to 17 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and the like.

The expression "optionally substituted benzyl" refers to a benzyl or benzyl substituted in 2-, 3-, 4-, 5- and/or 6-position by lower alkyl or lower alkoxy, such as 4-methylbenzyl, 4-methoxybenzyl, C-methylbenzyl and the like.

Lower alkyl means within the present invention the alkyl groups of straight or branched chain, containing from 1 to 5 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.-butyl, pentyl, isopentyl or tert.-pencil. The expression "lower alkoxy" denotes a group in which the alkyl radical has the previous value.

Aryl denotes in the framework of this application phenyl radical which may be unsubstituted or singly or multiply substituted in the position ortho, meta or para. As deputies are considered, in particular, lower alkyl or lower alkoxygroup or halogen, in particular chlorine. Particularly preferred aryl groups are phenyl and para-tolyl.

As the halogen or halide is used fluorine, chlorine, bromine or iodine, in particular chlorine, bromine or iodine.

The terms "halogenated lower alkyl" signifies in the framework of this application alkyl grupomania preferred halogenated lower alkyl groups are, for example, perfluorinated and perchloroethane lower alkyl groups, such as trifluoromethyl, Pentecostal and the like.

The terms "halogenated phenyl" denotes preferably perftoralkil or periorbital.

The expression "di(lower alkyl)amino" means in the context of the present invention, for example, dimethylamino, diethylamino and the like.

As protected groups to hydroxyl groups in the framework of the present invention are discussed, in particular, the usual groups forming a simple ester, as for example, benzyl, allyl, benzoyloxymethyl, lower alkoxymethyl or 2-methoxyethoxymethyl.

Cycloalkyl in the framework of the present invention comprises a cyclic alkyl group containing 5 to 8 carbon atoms, in particular cyclopentyl or cyclohexyl.

Substituted phenyl means in connection with the compounds of formulas IV and V is phenyl, substituted groups, electron donors, preferably in the 3rd 5-position, as, for example, groups of the formula

< / BR>
< / BR>
< / BR>
where

Y represents (-CH2-)m, oxygen, sulfur or N-R17,

A and a' independently of one another, indicates H2-, -CR13R14-, oxygen, certpaper, isobutyl, tert.-butyl, isopentyl or tert.-pencil), lower alkoxy (as methoxy, ethoxy), trialkylsilyl (as trimethylsilyl, triethylsilyl), cycloalkyl (as cyclopentyl, cyclohexyl, benzyl or one of the radicals R13or R14also denotes hydrogen,

R15denotes hydrogen, lower alkyl, lower alkoxy, trialkylsilyl (as trimethylsilyl or triethylsilyl), di(lower alkyl) amino or lower thioalkyl,

R17denotes lower alkyl, in particular methyl,

m denotes an integer of 1, 2 or 3.

The expression "five-membered heteroaromatic hydrocarbon" within this application denotes Deputy formula

< / BR>
< / BR>
< / BR>
< / BR>
In formulas Vl-d Vl-g

And denotes oxygen, sulfur or N-R17,

R16denotes hydrogen, lower alkyl, particularly methyl or lower alkoxy, in particular methoxy,

R17denotes lower alkyl, in particular methyl,

n denotes 0, 1 or 2.

Proposed invention the asymmetric hydrogenation of compounds of the formula II into compounds of the formula I is carried out in a suitable in conditions of a reaction inert organic solvent. As such solvents are considered, in particular, the lower the DAMI, as for example, methylene chloride, chloroform, phenyl and the like; or mixtures with simple ether, as for example, a simple diethyl ether, tetrahydrofuran or dioxane, in addition, apply a mixture of the above alcohols with esters, as for example, a complex ethyl ester acetic acid, or carboxylic acids, such as formic acid, acetic acid, and the like, or with ketones, such as acetone, methyl ethyl ketone or diethylketone, or with water.

Preferably the reaction is carried out in methanol, ethanol or isopropanol, or mixtures of such alcohols with the above-mentioned halogenated hydrocarbons, with the abovementioned ethers or also with water. For the proposed invention the method is suitable, in particular, the above-mentioned alcohols or mixtures as methanol/water or methanol/diethyl ether/tetrahydrofuran, and the like.

The hydrogenation is conducted preferably at a temperature in the range from approximately 0oC to 100oC, preferably in the temperature range from about 20oC to 80oC and at a pressure of about 1 to 100 bar, preferably from about 5 to 70 bar.

The molar ratio between gidriruemyi connect edocfile between about 10,000 and about 100.

The ligands of the formulae IV and V are known compounds or analogues of known compounds which can be easily obtained in a similar manner for obtaining the known ligands.

Compounds of formulas IV and V, where R8and R9are the same, can be obtained, for example, as described in European patent 104 375, as well as in the European patent 398 132. Obtaining compounds, where R8and R9differ from each other, is carried out in two stages, as described, for example, in European patent 543 245.

The complexes of formula III-B and III-c can be obtained in a known manner. The complexes of formula III-d can be obtained, for example, so that the compounds of formulas IV or V transform using connections that can give the ruthenium in a concentrated, inert organic or aqueous solvent. The complexes of formula III-a can be obtained from compounds III-d by transformation with HX, where X has the above meaning, in particular, BF-4or CF3SO-3.

Enantioselective hydrogenation of compounds of the formula II is preferably carried out in the presence of complexes of ruthenium-diphosphine formula III and, in particular, in prisutstvuet acid.

Ligand of formulas IV and V used in the present invention, preferred are ligands of the formula IV. Particularly preferred ligands of the formula IV are compounds where R5and R6are identical and represent methyl or methoxy, R is 0, and R8and R9have the same meaning and represent substituted phenyl, preferably a group of formula Vl-a, where R13and R14are identical and represent methyl, isopropyl, tert.-butyl, tert. pentyl, methoxy, trimethylsilyl or triethylsilyl, and R15denotes hydrogen, methoxy or dimethylamino.

Examples of particularly preferred ligands of the formula IV:

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,4,5-trimethoxyphenyl)- phosphine] (3,4,5-MeO-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-dimethyl-4-dimethylamino - phenyl)phosphine] (DMAXyl-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-bis(trimethylsilyl) -phenyl)phosphine] (3,5-TMS-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-bis(triethylsilyl) phenyl)phosphine] (3,5-TES-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-diisopropylphenyl) phosphine] (3,5-iPr-MeOBIPHEP)

(6,6' -dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-decret. - butylphenyl)phosphine] (3,5-tBu-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-the Nile)- phosphine] (Xyl-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-aminobutiramida 4 - methoxyphenyl)phosphine] (3,5-iPr-4-MeO-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-decret.-butyl-4 - methoxyphenyl)phosphine] (3,5-tBu-4-MeO-MeOBIPHEP)

(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-decret. pentyl-4 - methoxyphenyl)phosphine] (3,5-tPen-4-MeO-MeOBIPHEP)

The following examples serve to illustrate the invention and does not limit it. Used in these examples, the abbreviations have the following meanings:

SLA Acetoxy

Ehud Liquid chromatography high pressure

CT Room temperature

BB High vacuum: 0.1 mbar

GC 7 Capillary gas chromatography.

Sample products will acetimidoyl using acetanhydride/pyridine or similarbut using N,O-bis(trimethylsilyl)ndimethylacetamide/5% TCS in pyridine. Samples containing catalyst, dissolved in methylene chloride and the solution is filtered through a small amount of silica gel in order to separate the catalyst.

O. H. Optical purity of (R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-Piran-2-he, []2D0= -45,6oC (C=1, dioxane).

its Enantiomeric excess of 3-hexyl-5,6-dihydro-4-methoxy-6 - undecyl-2H-Piran-2-it. Simple methyl ether floor is rearview acid/methanol and p-toluenesulfonic acid as a catalyst. Determination of enantiomeric excess by using liquid chromatography high pressure (ghvd) in the phase Chiralcel-OD.

BPH 3-hexyl-5,6-dihydro-4-hydroxy-b-undecyl-2H-Piran-2-he (dihydropyran)

DGPM 3-hexyl-5,6-dihydro-4-methoxy-6-undecyl-2H-Piran-2-he (dihydropyran-simple methyl ether).

All temperatures are in degrees Celsius.

Example 1.

a) In the reactor Glove Box (argon, < 1 ppm oxygen) dissolved in 19.6 mg (0.06 mmol) of Di(2-acetato)-(4- cycloocta-1,5-diene)ruthenium(II) and 61.9 mg (to 0.060 mmol) (S)-3,5-tBu-MeOBIPHEP 7.5 ml simple diethyl ether and 2.5 ml of tetrahydrofuran in the tube and the solution is stirred at a temperature of 40oC during the night. After cooling, add 2.5 ml (0,015 mmol) of the catalyst solution of 6.5 ml of a simple diethyl ether/tetrahydrofuran (3:1, vol/vol) and the resulting solution is mixed with a solution of 26.3 mg (0.15 mmol) of 50% aqueous HBF47.5 ml of methanol. Yellow catalyst solution is stirred for 1.5 hours at room temperature.

b) In the reactor Glove Box placed AOR-ml autoclave with a glass nozzle with 1,05 g (3,00 mmole) of 3-hexyl-4-hydroxy-6-undecyl-2H-Piran-2-it, and 13.5 ml of methanol and Katalizator for 48 hours at a temperature of 60oC and a pressure of 60 bar.

Yellow hydrogenated solution is evaporated on a rotary evaporator at a temperature of 35oC and a pressure of 20 mbar. The residue (1,02 g of yellow crystals) consists, according to capillary GC-analysis of 59% C-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-Piran-2-it, 10% 3-hexyl-5,6-dihydro-4-methoxy-6-undecyl-2H-Piran-2-it, 5% of a mixture of 4 diastereoisomeric saturated lactones and 22% of the original substance. To determine the enantioselectivity 0.71 g of residue chromatographic on 40 g of silica gel. Methylene chloride aluinum 320 mg (R)-dihydropyrone, []2D0= -38,4oand after mixed fractions 27 mg of pure simple (R)-dihydropyran-methyl ester, 91,9% enantiomeric excess 3-hexyl-5,6-dihydro-4-methoxy-6-undecyl - 2H-Piran-2-it.

Example 2.

a) In the reactor Glove Box is stirred solution of 15.0 mg (0,012 mmol) of Ru(OAc)2[(S)-3,5-tBu-MeOBIPHEP) in 12.5 ml of methanol with a solution of 21.1 mg (0.12 mmol) of 50% aqueous HBF4in 2.5 ml of methanol and catalyst solution is stirred for 1.5 hours at room temperature.

b) In the reactor Glove Box put a 185 ml autoclave with 4,21 g (12.0 mmol) of 3-hexyl-4-hydroxy-6-undecyl-2H-Piran-2-it, 15 ml of methanol and catalyst solution (S/C 1'000) obtained according to a). Hydra is owls. After cooling, evaporated yellow crystalline solution at a temperature of 40oC and a pressure of 18 mbar on a rotary evaporator. The residue (4.3 g yellow kristalliset), consisting, according to capillary GC-analysis of 73% 3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-Piran-2-it, 20% 3-hexyl-5,6-dihydro-4-methoxy-6-undecyl-2H-Piran-2-it and 5% mixture of 4 diastereoisomeric saturated lactones, chromatographic on 150 g of silica gel. Methylene chloride aluinum 210 mg (R) - dihydropyrone, []2D0= -42,0o(92% optical purity), 3,44 g of mixed fractions, consisting of dihydropyran and dihydropyran-simple methyl ether, and 120 mg (R)-dihydropyran-simple methyl ester, to 92.1% enantiomeric excess 3-hexyl-5,6-dihydro-4-methoxy-6-undecyl-2H - Piran-2-it.

Example 22.

a) In the reactor Glove Box (argon, < 1 ppm oxygen) dissolved 13,1 mg (0,040 mmol)/ Di(2-acetato)-(4- cycloocta-1,5-di - ene)ruthenium(11) and 41.3 mg (0,040 mmol) of (S)-3,5-tBu-MeBIPHEP 2.25 ml simple diethyl ether and 0.75 ml of tetrahydrofuran in the tube Slinka and the solution is stirred overnight at a temperature of 40oC. After cooling, add a solution of 14 mg (0.08 mmol) of 50% aqueous HBF4in 2.5 ml of methanol. Yellow catalyst is l autoclave with a glass nozzle with 0.36 g (1.00 mmol) of 3-hexyl-4-methoxy-6-undecyl-2H-Piran-2-it, to 4.5 ml of methanol and catalyst solution obtained under a). The hydrogenation is carried out with stirring using a magnetic rod for 40 hours at a temperature of 60oC and a pressure of 60 bar.

Yellow hydrogenated solution is evaporated on a rotary evaporator at a temperature of 35oC at a pressure of 20 mbar. The residue (0.35 g yellow crystals) consists, according to the capillary TX-analysis of 71% C-hexyl - 5,6-dihydro-4-methoxy-6-undecyl-2H-Piran-2-she and 21% of the original substance. To determine the enantioselectivity solution of the residue is filtered in methylene chloride through a small amount of silica gel, and the eluate analyzed after evaporation using jhud: 53% enantiomeric excess C-hexyl-5,6-dihydro-4-methoxy-6-undecyl-2H-Piran-2-it.

Example 23.

a) In the reactor Glove Box, a solution of 16.4 mg (0,012 mmol) of Ru(OAc)2[(S)-3,5-tBu-4-MeO-MeOBIPHEP] in 12.5 ml of methanol is mixed with a solution of 13.7 mg (0.12 mmol) triperoxonane acid in 2.5 ml of methanol and catalyst solution is stirred for 1.5 hours at room temperature.

b) In the reactor Glove Box put a 185 ml autoclave with 4,21 g (12.0 mmol) of 3-hexyl-4-hydroxy-6-undecyl-2H-Piran-2-it, 15 ml of methanol and catalyst solution (S/C 1 '000) obtained according to a). G hours. After cooling, the yellow crystalline solution is evaporated on a rotary evaporator at a temperature of 40oC and a pressure of 18 mbar. The remainder of 4.2 g of a yellow kristalliset) consists, according to capillary GC-analysis of 46% of the original substance, 48% C-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-Piran-2-it and 1% mixture of 4 diastereoisomeric saturated lactones.

To determine the enantiomeric excess of 3-hexyl-5,6-dihydro-4 - methoxy-6-undecyl-2H-Piran-2-it is a mixture of handle complex with methyl ether of orthomorphisms acid/methanol and a catalytic amount of p-toluenesulfonic acid and analyzed by Ehud: 87,8% enantio - dimensional excess of 3-hexyl-5,6-dihydro-4-methoxy-6-undecyl-2H-Piran-2-it (R).

Example 24.

a) In the reactor Glove Box, a solution of 16.4 mg (0,012 mmol) of Ru(OAc)2[(S)-3,5-tBu-4-MeO-MeOBIPHEP] in 12.5 ml of methanol is mixed with a solution of 4.2 mg (0.024 mmol) of 50% aqueous HBF4in 2.5 ml of methanol and the solution is stirred for 1.5 hours at room temperature. Then add to 44.6 mg (0,096 mmol) performanceheavy acid and stirred catalyst solution within 15 minutes.

b) In the reactor Glove Box put a 185 ml autoclave with 4,21 g (12.0 mmol) of 3-hexyl-4-hydroxy-6-undecyl-2H-Piran-2-it, 15 ml of methanol and catalysate 60 bar and a strong stirring for 20 hours. After cooling, evaporated yellow crystalline solution on a rotary evaporator at a temperature of 40oC and a pressure of 18 mbar. The remainder of 4.2 g of a yellow kristalliset) consists, according to capillary GC-analysis of 51% of the initial substances, 44% C-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-Piran-2-it, 2% 3-hexyl-5,6-dihydro-4-methoxy-6-undecyl-2H-Piran-2-it and 1% mixture of 4 diastereoisomeric saturated lactones.

To determine the enantiomeric excess of 3-hexyl-5,6-dihydro-4 - hydroxy-6-undecyl-2H-Piran-2-it is a mixture of handle complex with methyl ether of orthomorphisms acid/methanol and a catalytic amount of p-toluenesulfonic acid and analyzed by Ehud: 92,8% enantiomeric excess 3-hexyl-5, b-dihydro-4-methoxy-6-undecyl - 2H-PYRAN-it (R).

1. The way enantioselective obtain optically active substituted derivatives of 5,6-dihydro-2H-Piran-2-it formula I

< / BR>
where R1and R2denote alkyl, which can be broken by oxygen atom in a different position than or position, or optionally substituted benzyl;

R3denotes hydrogen, lower alkyl, optionally substituted benzyl, -CO-R4, -COOR4or-CONR42;

R4denotes lower alkyl have the above significance, characterized in that the asymmetric hydrogenation is carried out in the presence of a complex of optically active atropoisomeric diphosphine-ligand with the metal of group VIII.

2. The method according to p. 1, wherein the asymmetric hydrogenation is carried out in the presence of one of the optically active complexes of ruthenium-diphosphine formulas

[RuL]2+(X)2III-a

[RuLX2-]2+(X)2III-b

[RuLX1X2]+X3III-c

RuL(X4)2III-d

where X denotes BF-4, ClO-4, B(phenyl)-4, SbF-6PF-6, Z1-SO-3,

X1denotes halogen;

X2denotes benzene, hexamethylbenzene or para-timol;

X3denotes a halide, ClO-4, B(phenyl)-4, SbF-6PF-6, Z1-SO-3BF-4;

X4denotes the anion Z2-COO-or the anion Z3-SO-3,

Z1denotes a halogenated lower alkyl or halogenated lower phenyl;

Z2denotes lower alkyl, phenyl, halogenated lower alkyl or halogenated lower phenyl;

Z3denotes n the crystals IV

< / BR>
or the General formula V

< / BR>
in (S)- or (R)-form,

where R5and R6independently of one another represent lower alkyl, lower alkoxy, di(lower alkyl)amino, hydroxyl group, protected hydroxyl group, hydroxymethyl or a protected hydroxymethyl, or

R5and R6together represent the divalent group

-(CH2)q-, -CH2-O-CH2-,

< / BR>
R7denotes hydrogen, lower alkyl or lower alkoxy;

R8and R9independently of one another denote cycloalkyl, unsubstituted or substituted phenyl or five-membered heteroaromatic hydrocarbon, provided that at least one of the radicals R8and R9represents a substituted phenyl ring or five-membered heteroaromatic hydrocarbon;

R10represents preferably in the 5,5'-position a halogen, hydroxyl group, lower alkyl, amino, acetamido, nitro or sulfo;

R11denotes lower alkyl, phenyl or benzyl;

R12denotes lower alkyl, or both R12are together di - or trimethylene;

p denotes 0 or the number 1, 2 or 3;

q denotes a number of 3, 4 or 5.

3. The method according to one of the active ruthenium complex-diphosphine formula III-a

[RuL]2+(X)2,

where X denotes

L denotes an optically active atropoisomeric ligand of formula IV

< / BR>
in (R)- or (S)-form,

where R5and R6are identical and represent methyl or methoxy;

p is 0,

R8and R9are the same and represent substituted phenyl.

4. The method according to one of paragraphs.1 to 3, wherein R8and R9optically active ligand of formula IV have the same meaning and represent a radical of the formula IV-a

< / BR>
where R13and R14independently of one another represent lower alkyl, lower alkoxy, trialkylsilyl, cycloalkyl, benzyl or one of the radicals R13or R14denotes hydrogen;

R15denotes hydrogen, hydroxyl group, lower alkyl, lower alkoxy, trialkylsilyl or di(lower alkyl)-amino.

5. The method according to p. 4, wherein R13and R14are identical and represent methyl, methoxy, isopropyl, tertbutyl, trepetin or trimethylsilyl, R15represents hydrogen or methoxy.

6. The method according to one of paragraphs.1 to 5, characterized in that the enantioselective hydrogenation of compounds of formula II implementation is 00oC.

7. The method according to one of paragraphs.1 - 6, characterized in that provide the compounds of formula I, where R1represents an alkyl group with a straight chain of from 5 to 17 carbon atoms, R2represents an alkyl group with a straight chain of from 1 to 7 carbon atoms and R3represents hydrogen, enantioselective hydrogenation of compounds of formula II in the presence of an optically active ruthenium-diphosphine complex of formula III-a.

 

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