The present invention relates to a process for enantioselectively hydrogenating prochiral ketones to (S)-alcohols using platinum catalysts in the presence of cinchonines or quinidines as modifiers and of hydrogen, which is characterized in that the modifiers used are cinchonines unsubstituted in the 3-position, 3-ethylidenyl- or 9-methoxycinchonines or derivatives thereof in which the quinoline ring is replaced by other rings.
The enantioselective hydrogenation of xcex1-ketoesters using platinum catalysts in the presence of cinchonidine or cinchonine and derivatives of these quinuclidines has been described by H.-U. Blaser et al. in Catalysis Today 37 (1997), pages 441 to 463. This publication also discloses that the enantioselectivity in the presence of cinchonidine for preparing (R)-alcohols is considerably higher than in the presence of cinchonine for preparing (S)-alcohols. The same observation is made by B. Txc3x6rxc3x6k et al. in Chem. Comm. (1999), pages 1725 to 1726 in the enantioselective hydrogenation of an xcex1-ketodiacetal. The hydrogenation of xcex1-ketoacetals is also described by M. Studer et al. in Chem. Comm. (1999), pages 1727 to 1728. In J. Am. Chem. Soc. (2000) 122, pages 12675 to 12682, H. U. Blaser describes the influence of modification of cinchona alkaloids on the hydrogenation of ethyl pyruvate using cinchona-modified platinum catalysts. It is established that the substitution in the 3-position of the quinuclidine radical has virtually no or only a small influence. In connection with the determination of the pKa values of cinchona alkaloids, C. Drzewiczak et al. in Polish J. Che., 67, 48ff (1993) mention 3-ethylidenecinchonine without specifying a synthesis or use.
It has now been found that, surprisingly, it is possible to achieve a distinctly higher catalyst activity and increased enantioselectivity in the hydrogenation of prochiral ketones to (S)-alcohols using hydrogen when platinum catalysts are modified with 3-ethylidene- or 9-methoxycinchonines or derivatives thereof in which the quinoline ring is replaced by other rings. The optical yields of (S)-alcohols may be over 90% ee and such high yields could hitherto be achieved in the preparation of (S)-alcohols by this hydrogenation route only by the use of ultrasound (B. Txc3x6rxc3x6k et al., Ultrasonics Sonochemistry 7 (2000) 151) or by continuously adding modifier (C. LeBlond et al., JACS 121 (1999) 4920).
The invention provides a process for enantioselectively hydrogenating prochiral ketones to (S)-alcohols using platinum catalysts in the presence of cinchonines or quinidines as modifiers and in the presence of hydrogen, which is characterized in that the modifiers used are cinchonines from the group of cinchonines unsubstituted in the 3-position, 3-ethylidenyl- or 9-methoxycinchonines or derivatives thereof in which the quinoline ring is replaced by other rings.
Prochiral ketones are well known. The prochiral xcex1-ketones may be saturated or unsaturated, open-chain or cyclic compounds which preferably have 5 to 30, more preferably 5 to 20, carbon atoms which are unsubstituted or substituted with radicals which are stable under the hydrogenation conditions. The carbon chain may be interrupted by heteroatoms, preferably from the group of xe2x80x94Oxe2x80x94, xe2x95x90Nxe2x80x94 and xe2x80x94NRxe2x80x2xe2x80x94, where Rxe2x80x2 is H, C1-C8-alkyl, preferably C1-C4-alkyl, C5-C8-cycloalkyl, for example cyclopentyl, cyclohexyl or cyclooctyl, C6-C10-aryl, for example phenyl or naphthyl, or C7-C12-aralkyl, for example phenylmethyl or phenylethyl. The prochiral ketones preferably have an activating group in the xcex1-position, for example a carboxyl, carboxylic ester, acetal, keto or ether group.
The prochiral ketones may be xcex1-ketocarboxylic acids, xcex1-ketocarboxylic esters, xcex1-ketoethers, xcex1-ketoacetals and xcex1,xcex2-diketones. These prochiral ketones may correspond to the formulae I, II, III, IV and V 
where
R1, R2, R3 and R6 are each independently a monovalent, saturated or unsaturated aliphatic radical having 1 to 12 carbon atoms, a saturated or unsaturated cycloaliphatic radical having 3 to 8 carbon atoms, a saturated or unsaturated heterocycloaliphatic radical having 3 to 8 ring members and one or two heteroatoms from the group of O, N and NRxe2x80x2, a saturated or unsaturated cycloaliphatic-aliphatic radical having 4 to 12 carbon atoms, a saturated or unsaturated heterocycloaliphatic-aliphatic radical having 3 to 12 carbon atoms and one or two heteroatoms from the group of O, N and NRxe2x80x2, an aromatic radical having 6 to 10 carbon atoms, a heteroaromatic radical having 4 to 9 carbon atoms and one or two heteroatoms from the group of O and N, an aromatic-aliphatic radical having 7 to 12 carbon atoms or a heteroaromatic-aliphatic radical having 5 to 11 carbon atoms and one or two heteroatoms from the group of O and N where Rxe2x80x2 is H, C1-C8-alkyl, preferably C1-C4-alkyl, C5- or C6-cycloalkyl, C6-C10-aryl, for example phenyl or naphthyl, C7-C12-aryl, for example phenylmethyl or phenylethyl,
R1 and R2 or R1 and R6 together are C1-C6-alkylene or C3-C8-1,2-cycloalkylene, or C2-C4-alkylene or C3-C8-cycloalkylene fused to 1,2-phenylene, and R3 is as defined above,
R2 and R3 together are C1-C6-alkylene, C1-C8-alkylidene, C3-C8-1,2-cycloalkylene, C3-C8-cycloalkylidene, benzylidene, 1,2-phenylene, 1,2-pyridinylene, 1,2-naphthylene, or C3-C4-alkylene or C3-C8-1,2-cycloalkylene fused to 1,2-cycloalkylene or 1,2-phenylene, and R1 is as defined above,
and R1, R2, R3 and R6 are each unsubstituted or substituted by one or more, identical or different radicals selected from the group of C1-C4-alkyl, C2-C4-alkenyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, C1-C4-alkoxymethyl or -ethyl, C1-C4-haloalkoxy, cyclohexyl, cyclohexyloxy, cyclohexylmethyl, cyclohexylmethyloxy, phenyl, phenyloxy, benzyl, benzyloxy, phenylethyl, phenylethyloxy, halogen, xe2x80x94OH, xe2x80x94OR4, xe2x80x94OC(O)R4, xe2x80x94NH2, xe2x80x94NHR4, xe2x80x94NR4R5, xe2x80x94NHxe2x80x94C(O)xe2x80x94R4, xe2x80x94NR4xe2x80x94C(O)xe2x80x94R4, xe2x80x94CO2R4, xe2x80x94CO2xe2x80x94NH2, xe2x80x94CO2xe2x80x94NHR4, xe2x80x94CO2xe2x80x94NR4R5 where R4 and R5 are each independently C1-C4-alkyl, cyclohexyl, cyclohexylmethyl, phenyl or benzyl.
The heterocyclic radicals are bonded via a ring carbon atom to the oxygen atoms or the carbon atom of the carbonyl groups in the compounds of the formulae I, II, III, IV and V.
Preferred substituents are methyl, ethyl, n- and i-propyl, n- and t-butyl, vinyl, allyl, methyloxy, ethyloxy, n- and i-propyloxy, n- and t-butyloxy, trifluoromethyl, trichloromethyl, xcex2-hydroxyethyl, methoxy- or ethoxymethyl or -ethyl, trifluoromethoxy, cyclohexyl, cyclohexyloxy, cyclohexylmethyl, cyclohexylmethyloxy, phenyl, phenyloxy, benzyl, benzyloxy, phenylethyloxy, phenylethyl, halogen, xe2x80x94OH, xe2x80x94OR4, xe2x80x94OC(O)R4, xe2x80x94NH2, xe2x80x94NHR4, xe2x80x94NR4R5, xe2x80x94NHxe2x80x94C(O)xe2x80x94R4, xe2x80x94NR4xe2x80x94C(O)xe2x80x94R4, xe2x80x94CO2R4, xe2x80x94CO2xe2x80x94NH2, xe2x80x94CO2xe2x80x94NHR4, xe2x80x94CO2xe2x80x94NR4R5 where R4 and R5 are each independently C1-C4-alkyl, cyclohexyl, cyclohexylmethyl, phenyl or benzyl.
The aliphatic radical is preferably alkyl which may be linear or branched and preferably has 1 to 8, more preferably 1 to 4, carbon atoms, or preferably alkenyl or alkynyl, each of which may be linear or branched and preferably have 2 to 8, more preferably 2 to 4, carbon atoms. When R2 and R3 are alkenyl or alkynyl, the unsaturated bond is preferably in the xcex2-position to the oxygen atom. Examples include methyl, ethyl, n- and i-propyl, n-, i- and t-butyl, pentyl, i-pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl, vinyl, allyl, ethynyl and propargyl. A preferred group of aliphatic radicals is methyl, ethyl, n- and i-propyl, n-, i- and t-butyl.
The cycloaliphatic radical is preferably cycloalkyl or cycloalkenyl having preferably 3 to 8, more preferably 5 or 6, ring carbon atoms. Some examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, and also cyclopentenyl, cyclohexenyl and cyclohexadienyl. Particular preference is given to cyclopentyl and cyclohexyl.
The heterocycloaliphatic radical is preferably heterocycloalkyl or heterocycloalkenyl having preferably 3 to 6 carbon atoms, 4 to 7 ring members and heteroatoms selected from the group of xe2x80x94Oxe2x80x94 and xe2x80x94NRxe2x80x2xe2x80x94 where Rxe2x80x2 is H, C1-C8-alkyl, preferably C1-C4-alkyl, C5- or C6-cycloalkyl, C6-C10-aryl, for example phenyl or naphthyl, phenyl or phenylethyl. Some examples are pyrrolidinyl, pyrrolinyl, tetrahydrofuranyl, dihydrofuranyl and piperazinyl.
The cycloaliphatic-aliphatic radical is preferably cycloalkyl-alkyl or -alkenyl having preferably 3 to 8, more preferably 5 or 6, ring carbon atoms, and preferably 1 to 4, or 2-4, more preferably 1 or 2, or 2 or 3, carbon atoms in the alkyl group and alkenyl groups respectively. Examples include cyclopentyl- or cyclohexylmethyl or -ethyl and cyclopentyl- or cyclohexylethenyl.
The heterocycloaliphatic-aliphatic radical is preferably heterocycloalkyl-alkyl or -alkenyl having preferably 3 to 6 carbon atoms, 4 to 7 ring members and heteroatoms selected from the group of xe2x80x94Oxe2x80x94 and xe2x80x94NRxe2x80x2xe2x80x94 where Rxe2x80x2 is H, C1-C8-alkyl, preferably C1-C4-alkyl, C5- or C6-cloalkyl, C6-C10-aryl, for example phenyl or naphthyl, phenyl or phenylethyl, and preferably 1 to 4, more preferably 1 or 2, carbon atoms in the alkyl group and 2 to 4, more preferably 2 or 3, carbon atoms in the alkenyl group. Examples include pyrrolidinylmethyl or -ethyl or -ethenyl, pyrrolinylmethyl or -ethyl or -ethenyl, tetrahydrofuranylmethyl or -ethyl or -ethenyl, dihydrofuranylmethyl or -ethyl or -ethenyl, and piperazinylmethyl or -ethyl or -ethenyl.
The aromatic radicals are preferably naphthyl and in particular phenyl.
The aromatic-aliphatic radicals are preferably phenyl- or naphthyl-C1-C4-alkyl or -C2-C4-alkenyl. Some examples are benzyl, naphthylmethyl, xcex2-phenylethyl and xcex2-phenylethenyl.
The heteroaromatic radicals are preferably 5- or 6-membered, optionally fused ring systems. Some examples are pyridinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furanyl, oxazolyl, imidazolyl, benzofuranyl, indolyl, benzimidazolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl.
The heteroaromatic-aliphatic radicals are preferably 5- or 6-membered, optionally fused ring systems which are bonded via one of their carbon atoms to the free bond of an alkyl group or alkenyl group where the alkyl group preferably contains 1 to 4, more preferably 1 or 2, carbon atoms, and the alkenyl group preferably contains 2 to 4, more preferably 2 or 3, carbon atoms. Some examples are pyridinylmethyl or ethyl or -ethenyl, pyrimidinylmethyl or -ethyl or -ethenyl, pyrrolylmethyl or -ethyl or -ethenyl, furanylmethyl or -ethyl or -ethenyl, imidazolylmethyl or -ethyl or -ethenyl, indolylmethyl or -ethyl or -ethenyl.
R6 is preferably an aliphatic, cycloaliphatic or araliphatic radical, and more preferably linear C1-C4-alkyl.
More preferred compounds of the formulae I, II, III, IV and V include those where
R1, R2, R3 and R6 are each independently linear or branched C1-C8-alkyl, C4-C7-cycloalkyl or C4-C6-heterocycloalkyl having heteroatoms from the group of O and N, C6-C10-aryl or C4-C9-heteroaryl having heteroatoms from the group of O and N, C4-C7-cycloalkyl-C1-C4-alkyl or C3-C6-heterocycloalkyl-C1-C4-alkyl having heteroatoms from the group of O and N, C6-C10-aryl-C1-C4-alkyl or C4-C9-heteroaryl-C1-C4-alkyl having heteroatoms from the group of O and N,
R1 and R2 or R1 and R6 together are C1-C4-alkylene or C4-C7-1,2-cycloalkylene, or C2-C4-alkylene or C4-C7-cycloalkylene fused to 1,2-phenylene, and R3 is as defined above,
R2 and R3 together are C1-C4-alkylene, C1-C4-alkylidene, C4-C7-1,2-cycloalkylene, C4-C7-cycloalkylidene, benzylidene, 1,2-phenylene, 1,2-pyridinylene, 1,2-naphthylene, or C3-C4-alkylene or C4-C7-cloalkylene fused to 1,2-cycloalkylene or 1,2-phenylene, and R1 is as defined above
where R1, R2, R3 and R6 are each unsubstituted or substituted by one or more, identical or different radicals selected from the group of C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, C1-C4-alkoxymethyl or -ethyl, C1-C4-haloalkoxy, cyclohexyl, cyclohexyloxy, cyclohexylmethyl, cyclohexylmethyloxy, phenyl, phenyloxy, benzyl, benzyloxy, phenylethyl, phenylethyloxy, halogen, xe2x80x94OH, xe2x80x94OR4, xe2x80x94OC(O)R4, xe2x80x94NH2, xe2x80x94NHR4, xe2x80x94NR4R5, xe2x80x94NHxe2x80x94C(O)xe2x80x94R4, xe2x80x94NR4xe2x80x94C(O)R4, xe2x80x94CO2R4, xe2x80x94CO2xe2x80x94NH2, xe2x80x94CO2xe2x80x94NHR4, xe2x80x94CO2xe2x80x94NR4R5 where R4 and R5 are each independently C1-C4-alkyl, cyclohexyl, phenyl or benzyl.
A preferred subgroup of the compounds of the formulae I, II, III, IV and V are those where
R1, R2, R3 and R6 are each independently linear or branched C1-C4-alkyl, C2-C4-alkenyl, C5-C6-cycloalkyl, phenyl, phenylethenyl, C5-C6-cycloalkyl-C1-C2-alkyl, or C6-C10-aryl-C1-C2-alkyl,
R1 and R2 or R1 and R6 together are C1-C3-alkylene or C5-C6-1,2-cycloalkylene,
R2 and R3 together are C2-C4-alkylene, C1-C4-alkylidene, C5-C6-1,2-cycloalkylene, C5-C6-cycloalkylidene, benzylidene, 1,2-phenylene
where R1, R2, R3 and R6 are each unsubstituted or substituted as defined previously.
A particularly preferred subgroup of the compounds of the formulae I, II, III, IV and V are those where
R1 and R6 are each C1-C4-alkyl, C2-C4-alkenyl, cyclohexyl, phenyl, benzyl, phenylethyl or phenylethenyl,
R2 and R3 are each independently linear or branched C1-C4-alkyl, cyclohexyl, phenyl, benzyl or phenylethyl,
R1 and R2 or R1 and R6 together are C2-C3-alkylene or 1,2-cyclohexylene,
R2 and R3 together are C2-C3-alkylene, C1-C4-alkylidene, 1,2-cyclohexylene, cyclohexylidene, benzylidene or 1,2-phenylene
where R1, R2, R3 and R6 are each unsubstituted or substituted by methyl, ethyl, n- and i-propyl, n- and t-butyl, vinyl, allyl, methyloxy, ethyloxy, n- and i-propyloxy, n- and t-butyloxy, trifluoromethyl, trichloromethyl, xcex2-hydroxyethyl, methoxy- or ethoxymethyl or -ethyl, trifluoromethoxy, cyclohexyl, cyclohexyloxy, cyclohexylmethyl, cyclohexylmethyloxy, phenyl, phenyloxy, benzyl, benzyloxy, phenylethyloxy, phenylethyl, halogen, xe2x80x94OH, xe2x80x94OR4, xe2x80x94OC(O)R4, xe2x80x94NH2, xe2x80x94NHR4, xe2x80x94NR4R5, xe2x80x94NHxe2x80x94C(O)xe2x80x94R4, xe2x80x94NR4xe2x80x94C(O)xe2x80x94R4, xe2x80x94CO2R4, xe2x80x94CO2xe2x80x94NH2, xe2x80x94CO2xe2x80x94NH4, xe2x80x94CO2xe2x80x94NR4R5 where R4 and R5 are each independently C1-C4-alkyl, cyclohexyl, cyclohexylmethyl, phenyl or benzyl.
Some of the compounds of the formulae I, II, III, IV and V are known or can be prepared in a manner known per se by means of similar processes.
The compounds of the formulae I, II, III, IV and V are hydrogenated to chiral secondary alcohols of the formulae VI, VII, VIII and IX 
where R1, R2, R3 and R6 are each as previously defined and the symbol * represents predominantly the S-form of one of the stereoisomers.
Platinum catalysts are known, extensively described and commercially available. It is possible to use either platinum in metal form, for example as a powder, or, which is preferred, platinum metal applied to finely divided supports. Examples of suitable supports include carbon, metal oxides, for example SiO2, TiO2, Al2O3, metal salts, and natural or synthetic silicates. The catalyst may also be a platinum colloid. The amount of platinum metal on the support may be, for example, 1 to 10% by weight, preferably 3 to 8% by weight, based on the support. Before their use, the catalysts may be activated by treating with hydrogen at elevated temperature and/or with ultrasound. Preferred catalysts are platinum on Al2O3.
The cinchonines unsubstituted in the 3-position, 3-ethylidenyl- or 9-methoxycinchonines or derivatives thereof to be used according to the invention may, for example, correspond to the formula XI with 8(R),9(S)-configuration 
where
R9 is CH2xe2x95x90CHxe2x80x94 or CH3CH2xe2x80x94 and R7 is methyl, or
R9 is H or CH3xe2x80x94CHxe2x95x90 and R7 is H or methyl, and
R8 is unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C14-aryl or C5-C13-heteroaryl having heteroatoms selected from the group of xe2x80x94Nxe2x95x90, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94 and xe2x80x94N(C1-C4-alkyl)-.
R8 as aryl and heteroaryl may be a monocyclic or fused polycyclic radical having preferably 2 or three rings. The rings preferably contain 5 or 6 ring members. Some examples are phenyl, furyl, thiophenyl, N-methylpyrrolyl, pyridinyl, naphthyl, tetrahydronaphthyl, anthracenyl, phenanthryl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, indenyl, fluorenyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, dihydrobenzothiophenyl, N-methylindolyl, dihydro-N-methylindolyl, dibenzofuranyl, dibenzothiophenyl and N-methylcarbazolyl.
The cinchonines unsubstituted in the 3-position, 3-ethylidenyl- or 9-methoxycinchonines or derivatives thereof to be used according to the invention preferably correspond to the formula XIa with 8(R),9(S)-configuration 
where
R9 is CH2xe2x95x90CHxe2x80x94 or CH3CH2xe2x80x94 and R7 is methyl, or
R9 is H or CH3xe2x80x94CHxe2x95x90 and R7 is H or methyl,
R8 is a radical of the formulae 
and R10 is H, OH or C1-C4-alkoxy.
R10 is preferably H, OH or methoxy.
The compounds of the formula XI where R9 is CH2xe2x95x90CHxe2x80x94 or CH3CH2xe2x80x94 and R7 is methyl may be prepared in a simple manner by methylating the hydroxyl group bonded to C9 of appropriate natural cinchona alkaloids. Compounds where R9 is ethyl are obtainable by hydrogenating the R9 vinyl group.
The compounds of the formula XI where R9 is CH3xe2x80x94CHxe2x95x90 may be prepared by isomerizing the R9 vinyl group in the presence of metal complexes, for example ruthenium/phosphine complexes. An implementation of the process is described in the examples. In general, mixtures of the Z- and E-isomers are obtained which can be used directly as such.
The compounds of the formula XI which are not derived from natural cinchonines are synthetically accessible, for example, by means of reacting quinuclidine N-oxide with lithium alkyls (Li-methyl or Li-n-butyl) with aldehydes R8xe2x80x94CHxe2x95x90O, subsequent reaction with a Lewis acid, for example TiCl3, and ensuing alkaline hydrolysis. The diastereomers may be separated chromatographically on silica gel, and the enantiomers may be separated chromatographically on chiral columns. This is described in more detail in the examples.
The platinum metal may be used, for example, in an amount of 0.01 to 10% by weight, preferably 0.05 to 10% by weight and more preferably 0.1 to 5% by weight, based on the prochiral ketone used, although amounts of 0.1 to 3% by weight, or 0.1 to 1% by weight generally suffice. The increased activity of the hydrogenation system to be used according to the invention allows smaller total amounts of catalyst, which makes the process more economic.
The modifier may be used, for example, in an amount of 0.1 to 10 000% by weight, preferably 1 to 500% by weight and more preferably 10 to 200% by weight, based on the platinum metal used. The modifier may be introduced into the reaction vessel together with the platinum metal catalyst, or the platinum metal catalyst may be impregnated beforehand with the modifier.
The hydrogenation is preferably carried out under a hydrogen pressure of up 200 bar, more preferably up to 150 bar and particularly preferably 10 to 100 bar.
The reaction temperature may be, for example, xe2x88x9250 to 100xc2x0 C., more preferably 0 to 50xc2x0 C. and particularly preferably 0 to 35xc2x0 C. It is generally possible to achieve better enantioselectivies at low temperatures.
The reaction may be carried out without or in an inert solvent or mixtures of solvents. Examples of suitable solvents include aliphatic, cycloaliphatic and aromatic hydrocarbons (pentane, hexane, petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, xylene), ethers (diethyl ether, dibutyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, dioxane), water, alcohols (methanol, ethanol, propanol, butanol, ethylene glycol, diethylene glycol, ethylene glycol monomethyl or monoethyl ether, diethylene glycol monomethyl or monoethyl ether), ketones (acetone, methyl isobutyl ketone), carboxylic esters and lactones (ethyl or methyl acetate, valerolactone), N-substituted carboxamides and lactams (dimethylformamide, N-methylpyrrolidone), and carboxylic acids (acetic acid, propionic acid, butyric acid). The choice of the solvent may be used to influence the optical yield. For example, aromatic hydrocarbons (benzene, toluene, xylene) have proven particularly useful in the case of xcex1-ketoacetals and aromatic xcex1-ketocarboxylic esters, while better results can be achieved using carboxylic acids, for example acetic acid, in the case of aliphatic xcex1-ketocarboxylic acids.
The process according to the invention may, for example, be carried out in such a way that the catalyst is initially charged in an autoclave with the nitrogen base, optionally with a solvent, then the prochiral xcex1-ketone is added, then the air is displaced with an inert gas, for example noble gases, hydrogen is injected in and then the reaction is started, optionally with stirring or shaking, and hydrogenation is effected until no more hydrogen takeup is observed. The xcex1-hydroxyl compound formed may be isolated and purified by customary methods, for example distillation, crystallization and chromatographic methods.
The invention also provides compounds of the formula XIb 
where
R9 is CH2xe2x95x90CHxe2x80x94 or CH3CH2xe2x80x94 and R7 is methyl, or
R9 is H or CH3xe2x80x94CHxe2x95x90 and R7 is H or methyl, and
R10 is H or C1-C4-alkoxy.
When R7 is H, R10=H and R9 is CH2xe2x95x90CHxe2x80x94, the molecule is cinchonine (Cn) and when R7 is H, R10=H and R9 is CH3CH2xe2x80x94, the molecule is hydrocinchonine (HCn).
The (S)-xcex1-alcohols which can be prepared according to the invention are valuable intermediates for the preparation of natural active ingredients (B. T. Cho et al. in Tetrahedron: Asymmetry Vol. 5, No. 7 (1994), pages 1147 to 1150), and synthetic active pharmaceutical ingredients and pesticides. The (S)-xcex1-alcohols obtainable may be converted beforehand by known processes to derivatives which may then be used as intermediates for the preparation of active ingredients. The acid hydrolysis of, for example, xcex1-ketoacetals leads to 1,4-dioxanes or the corresponding aldehydes which are either hydrogenated to 1,2-diols having a secondary optically active hydroxyl group, or reacted with amines in the presence of phenylboric acids to optionally substituted optically active 1-phenyl-1-amino-2-hydroxyalkanes. After the protection of the OH group, for example by reaction with benzyl bromide, the hydroxyl-protected aldehydes may be obtained by reacting with strong acids and may be hydrogenated to 1,2-diols or converted to S-xcex1-hydroxycarboxylic acids by oxidation (for example with chromium trioxide) and removing the protecting group.