MXPA99008650A - Transfer hydrogenation process and catalyst - Google Patents

Abstract

A catalytic transfer hydrogenation process is provided. The catalyst employed in the process is a metal cyclopentadienyl complex which is coordinated to defined bidentate ligands. Preferred metals include rhodium, ruthenium and iridium. Preferred bidentate ligands are diamines and aminoalcohols, particularly those comprising chiral centres. The hydrogen donor is advantageously a secondary alcohol or a mixture of triethylamine and formic acid. The process can be employed to transfer hydrogenate ketones and imines, which are preferably prochiral. Catalysts for use in such a process are also provided.

Description

PROCESS AND CATALYST FOR TRANSFER HYDROGENATION The invention relates to hydrogenation by catalytic transfer, particularly in the presence of a transition metal complex, for a catalyst for such hydrogenation and a process for making optically active compounds. Hydrogenation by hydrogen transfer using catalysts containing nitrogen or phosphorus ligands is reexamined in detail by Zassinovich et al. in Chem. Rev., 1992.92, 1051-1069. These authors conclude "despite excellent results, much work remains to be done" Hydrogenation has been explored by transfer using catalysts in which the transition metal is coordinated to a hydrocarbon benzenoid. The following publications are of interest: (1) Noyori et al., JACS, 1995, 117, 7562-7563: describes the use of chloro-ruthenium-mesitylene-N-monotosyl-1,2-diphenylethylene diamine as a catalyst in the Hydrogenation by transfer of acetophenone to 1-phenylethanol by means of -propan-2-ol increases up to 95% the production having an excess REF .: 31300 enantiomer of 97%. Similar results are obtained starting from other alkylaryl ketones. The efficiency of the corresponding catalyst containing benzene in place of estylene is more sensitive to substituents in the aryl group of the initial ketone. The reaction times are usually rather prolonged, typically 15h, in reactions of longer time the stereoselectivity decreases, apparently due to reverse hydrogenation. No production numbers are reported. The authors comment that "the complete catalytic performance is capable of competing with the best current hydrogenation method" as described in a current publication of themselves. (2) Noyori et al., Soc. Chem. Commun., 1996, 233-234: which describes catalysts similar to those of Noyori et al (1) _ above, but containing other alkylbenzene ligands and various beta-alcohols -amino instead of diphenylethylene diamine differ from the effective extent in the hydrogenation of acetophenone. The beta-amino alcohol ligand gives greater catalytic stability. The preferred arene ligand is hexamethylbenzene. The renewal numbers are greater than 227 moles of product per mole of catalyst per hour. (3) Noyori et al., J.A.C.S., 1996, 118, 2521-2522: which describes that to prevent the transfer of inverse hydrogen in the process of Noyori et al. (1) above, triethylamine acid is used as the source of hydrogen; no production numbers are reported. (4) Noyori et al., J.A.C.S., 1996, 118, 4916-4917: which describes that the process of Noyori et al. (3) above, it is effective for the reduction of imines (especially cyclic imines) for enantioselected amines. These processes seem to require relatively long time cycles. As well as the non-economic fact of the use of a chemical plant, such slow reaction can be directed for the decomposition of the catalytic complex and slow loss of the optical purity of the product; moreover this gives a limited scope to adjust the reaction conditions such as temperature and reagent concentration to maximize the difference in proportion between a desired and undesired enantiomerically reaction. In addition, the linked phosphorus, nitrogen and benzene transition metal complexes based on pentamethylcyclopentadienyl (hereinafter Cp *) have been shown to be effective as catalysts in homogeneous hydrogenation of olefins by means of free hydrogen (Maitlis, Acc. Chem. Res., 1978, 11, 301-307; Maitlis et al., J. Chem. Soc. Dalton, 1978, 617-626); there is no disclosure of hydrogen transfer in the absence of free hydrogen or of catalyst containing a chelating or chiral targeting ligand. Iridium complexes with Cp * and carboxylic acid amino-alpha-sulfonylated or acylated by Grotjahn et al. (J.A.C.S., 1994, 116, 6969-6970) but without the evidence of catalytic activity. Rhodium complexes with Cp * and 2, 2-bipyridyls have been described and the use of these in a format to hydrogenate nicotinamide adenine dinucleotides (NAD) to NADH by Steckham et al. (Angew, Chem. Int. Ed. Engl., 1990, 29 (4), 388-390). Production frequencies of up to 67.5 per hour are reported, but activity is not reported after 100 catalytic cycles. We have discovered that hydrogenation by stereoselective transfer can be carried out efficiently by means of a catalyst comprising a complex of a transition metal, a chelating ligand and a cyclopentadienyl group.

According to a first aspect of the present invention there is provided a process for the hydrogenation by transfer of a compound of formula (1) to produce a compound of formula (2) < 1 > (2) wherein: X represents CR3R4, NR5, (NR5R5) + Q ", 0 or S; R, R, R, R, R and R each independently represents a hydrogen atom, an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclic group, one or more of R1 &R2, R1 &R3, R2 &R4, R3 &R4, R1 &R5, R2 &R6, and R5 &R6 are linked in a manner optionally so that an optionally substituted ring (s) is formed, and Q ~ represents an anion; said process comprises the reaction of the compound of formula (1) with a hydrogen donor in the presence of a catalyst, characterized in that the catalyst has the general formula: wherein: R7 represents an optionally substituted cyclopentadienyl group; A represents -NR8, -NR9, -NHR8 or -NR8R9 wherein R8 is H, C (0) R10, S02Ro, C (O) NR10R14, C (S) NR10R14, C (= NR14) SR15, or C ( = NR14) OR15, R9 and R10 each independently represents an optionally substituted hydrocarbyl, a perlogenated hydrocarbyl or an optionally substituted heterocyclic group, and R1 and R15 each independently represents hydrogen or a group as defined for R10.; B represents -0-, -OH, OR11, -S-, -SH, SR11, NR11- -NR > 1"2 -, -NHR> 12" or -NR> lJ "ltR > 1-2 where R1 is H, C (0) R .13, S02R > 13 C (0) NR13R16, C (S) NR13R16, C (= NR16) SR17 or C (= NR16) OR17, R11 and R13 each independently represents an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclic group , and R16 and R17 each independently represents hydrogen or a group as defined for R13; "E represents a linking group, M represents a metal capable of hydrogenation by catalytic transfer, and Y represents an anionic group, a basic ligand or a vacant site, provided that when Y is not a vacant site at least one of A or B carries a hydrogen atom It is believed that the catalyst species which are substantially represented in the above formula can be introduced on a solid support The hydrocarbyl groups which can be represented by R 1"6, R 9, R 10, R 11 and R13-17 which independently include alkyl, alkenyl, and aryl groups, as well as any combination thereof, such as aralkyl and alkaryl, for example benzyl groups.

Alkyl groups which may be represented by R 1-6, R 9, R 10, R 11 and R 13"17 include straight or branched chain alkyl groups comprising above 20 carbon atoms, particularly from 1 to 7 carbon atoms and preferably from 1 to 5 carbon atoms When the alkyl groups are branched, the groups often comprise up to 10 branched chain carbon atoms, preferably up to 4 branched chain atoms In certain embodiments, the alkyl group can be cyclic, commonly comprises from 3 to 10 carbon atoms in the largest ring and optionally contains one or more rings forming bridges Examples of alkyl groups that may be represented by R 1-6, R 9, R 10, R 11 and R 13"17 include methyl, ethyl , propyl, 2-propyl, butyl, 2-butyl, t-butyl and cyclohexyl groups. The alkenyl groups can be represented by R 1"6, R 9, R °, R 11 and R 13" 17 include alkenyl groups of 2 to 20 carbon atoms and preferably 2 to 6 carbon atoms. Double bonds of carbon atoms can occur. The alkenyl group may carry one or more substituents, particularly phenyl substituents. Examples of alkenyl groups include vinyl, styryl, and indenyl groups. When either R1 or R2 represents an alkenyl group, a carbon-carbon double bond is preferably located in the β-position to the radical C = X. When any of R1 or R2 represents an alkenyl group, the compound of formula (1) is preferably an α, β-unsaturated ketone. The aryl groups that may be represented by R1-6, R9, R10, R11 and R13"17 may contain 1 or 2 rings or more fused rings which may include cycloalkyl, aryl or heterocyclic rings Examples of aryl groups that may be represented by R1"6, R9, R10, R11 and R13 ~ 17 include phenyl, tolyl, fluorophenyl, chlorophenyl, bromophenyl, trifluoromethylphenyl, anisyl, naphthyl and ferrocenyl groups. Perhalogenated hydrocarbyl groups that can be represented by R 1"6, R 9, R 10, R 11 - and R 13-17 independently include perhalogenated aryl and alkyl groups, as well as any combination thereof, such as alkaryl and aralkyl groups. alkyl perhalogenates which can be represented by R1"6, R9, R10, R11 and R13" 17 include -CF3 and -C2F5.

Heterocyclic groups that can be represented by R1"6, -R9, R10, R11 and R13" 17 independently include saturated and partially unsaturated, aromatic ring systems, and which may constitute 1 or 2 rings or more fused rings which may include rings heterocyclic, aryl or cycloalkyl. The heterocyclic group contains at least one heterocyclic ring, the largest of which commonly comprises from 3 to 7 ring atoms in which at least one atom is carbon and at least one atom is any, N, O, S or P When any of R1 or R2 represents or comprises a heterocyclic group, the atom in R1 or R2 linked to the group C = X is preferably a carbon atom. Examples of heterocyclic groups that are represented by R 1"6, R 9, R 10, R 11 and R 13" 17 include pyridyl, pyrimidyl, pyrrolyl, thiophenyl, furanyl, indolyl, quinolyl, isoquinolyl, imidazoyl, and triazoyl groups. When any of R, R, R > ? o, R > n and R, 13-17 is a heterocyclic or substituted hydrocarbyl group, the substituent (s) must be ones that do not adversely affect the speed or stereoselectivity of the reaction. Optional substituents include halogen, cyano, nitro, hydroxy, amino, thiol, acyl, hydrocarbyl, perhalogenated hydrocarbyl, heterocyclic, hydrocarbyloxy, mono- or di-hydrocarbylamino, hydrocarbyl, esters, carbonates, amides, sulfonyl and sulfonamide groups wherein the hydrocarbyl groups are as defined for R1, above. One or more substituents may be present. When any of R1 & R2, R1 & R3, R2 '& R4, R3 & R4, R1 & R5, R2 & R6, and R5 & R6 are linked in such a way that when they are joined together with either the carbon atom and / or atom X of the compound of the formula (1) a ring is formed, it is preferred that these be rings of 5, 6 or 7 members . Examples of such compounds of formula (1) include 3,4-dihydroisoquinoline, 1-tetralone, 2-tetralone, 4-chromanone, -l-? T? Ethyl-6,7-dimethoxy-3, 4 dihydroisoquinoline, 1- benzosubarone, 2-indanone and 1- indanone. Compounds of formula (1) wherein X is represented by NR5 or (NR5R6) + Q ~, include imines or imino salts. Wherein a compound of formula (1) is • an imine, this can optionally be converted into an imino salt. Imine salts are more preferred than imines. Preferred imino salts are represented by compounds of the formula (1) in which X is (NR5R6) + Q ~ so that either R5 ^ or R6 is hydrogen but R5 or R6 are not identical. When the compound of formula (1) is an imino salt, an anion is represented by + Q ~ Examples of anions that may be present are halide, acid sulfate, tosylate, formate, acetate, tetrafluoroborate, trifluoromethanesulfonate and trifluoroacetate. It is more preferable that X is O. In certain preferred embodiments, R1 and R2 are both independently alkyl of 1 to 6 carbon atoms, both independently aryl, particularly phenyl, or one is aryl, particularly phenyl and one is alkyl of 1 to 6. carbon atoms. Substituents may be present, particularly substituents for the C = X group when one or both of R1 and R2 is a phenyl group. More advantageously, the compound of the formula (1) is prochiral, so that the hydrogenated product of the formula (2) comprises a chiral atom for which R1 and R2 and X are each linked. Such an asymmetric transfer hydrogenation process forms an especially preferred aspect of the present invention. More commonly, when the compound of the formula (1) is prochiral, and R1 and R2 are different, and none is hydrogen. Advantageously, one of R1 and R2 is an aliphatic and the other is aryl or heterocyclic. Examples of compounds of formula (1) include acetophenone, 4-chloroacetophenone, 4-methoxyacetophenone, 4-trifluoromethylacetophenone, 4-nitroacetophenone, 2-chloroacetophenone and acetophenone benzylimine. Hydrogen donors include hydrogen, primary and secondary alcohols, primary and secondary amines, carboxylic acids and their esters as well as amine salts, easily dehydrogenatable hydrocarbons, clean reduction agents, and any combination thereof. The primary and secondary alcohols which can be used as hydrogen donors commonly comprise from 1 to 10 carbon atoms, preferably from 2 to 7 carbon atoms, and more preferably from 3 to 4 carbon atoms. Examples of primary and secondary alcohols that can be represented as hydrogen donors include methanol, ethanol, propan-1-ol, propan-2-ol, butan-2-ol, cyclopentanol, cyclohexanol, benzyl alcohol, and menthol. When the donor is an alcohol, secondary alcohols are preferred, especially propan-2-ol and _butan-2-ol. The primary and secondary amines that can be used as hydrogen donors commonly comprise from 1 to 20 carbon atoms, preferably from 2 to 14 carbon atoms, and more preferably from 3 to 8 carbon atoms. Examples of primary and secondary amines that can be represented as hydrogen donors include ethylamine, propylamine, isopropylamine, butylamine, isobutylamine, hexylamine, diethylamine, dipropylamine, di-isopropylamine, dibutylamine, di-isobutylamine, dihexylamine, benzylamine, dibenzylamine and piperidine. . When the hydrogen donor is an amine, primary amines are preferred, especially primary amines comprising a secondary alkyl group, particularly isopropylamine and isobutylamine. The carboxylic acids or their esters which can be used as hydrogen donors commonly comprise from 1 to 10 carbon atoms, preferably from 1 to 3 carbon atoms. In certain embodiments, the carboxylic acid is advantageously a beta-hydroxy carboxylic acid. Esters can be derived from the carboxylic acid and an alcohol of 1 to 10 carbon atoms. Examples of carboxylic acids that can be used as hydrogen donors include formic acid, lactic acid, ascorbic acid and mandelic acid. When a carboxylic acid is used as a hydrogen donor, at least some carboxylic acid is preferably present as an amine salt or ammonium salt. The amines that can be used to form such salts include both amines, the aromatics and the non-aromatics, in addition to the primary, secondary and tertiary amines and typically comprising from 1 to 20 carbon atoms. Tertiary amines, especially trialkylamines, are preferred. Examples of amines that can be used to form salts include tri-ethylamine, triethylamine, di-isopropylethylamine and pyridine. The most preferred amine is triethylamine. When at least some carboxylic acid such as an amine salt is present, particularly when a mixture of formic acid and triethylamine is employed, the molar ratio of the acid to the amine is commonly about 5: 2. This proportion can be maintained during the course of the reaction by the addition of any component, but usually by the addition of the carboxylic acid.

The readily dehydrogenatable hydrocarbons that can be employed as hydrogen donors comprise hydrocarbons that have a propensity to aromatize or hydrocarbons that have a propensity to form highly conjugated systems. Examples of readily dehydrogenatable hydrocarbons that can be employed as hydrogen donors include cyclohexadiene, cyclohexane, tetralin, dihydrofuran, and the tees. _ Clean reduction agents that can be represented as hydrogen donors include reduction agents with a high reduction potential, particularly those that have a relative reduction potential to the standard hydrogen electrode of greater than about -0.1 eV, a often greater than about -0.5 eV, and preferably greater than about -1 eV. Examples of clean reduction agents that can be represented as hydrogen donors include hydrazine and hydroxylamine. The most preferred hydrogen donors are propan-2-ol, butan-2-ol, the triethylammonium formate and a mixture of formic acid and triethylammonium formate.

The optionally substituted cyclopentadienyl group that may be represented by R7 includes the cyclopentadienyl groups capable of an eta-5 linkage. The cyclopentadienyl group is often substituted with from 1 to 5 hydrocarbyl groups, preferably with 3 to 5 hydrocarbyl groups and more preferably with 5 hydrocarbyl groups. Preferred hydrocarbyl substituents include methyl, ethyl and phenyl. When the hydrocarbyl substituents contain enantiomeric and / or diastereomeric centers, it is preferred to use these enantiomerically and / or diastereomerically purified forms. Examples of optionally substituted cyclopentadienyl groups include cyclopentadienyl, pentamethylcyclopentadienyl, pentafenilciclopentadienilo, tetrafenilciclopentadienilo, etiltetrametilpentadienilo, mentiltetrafenilciclopentadienilo, neomentiltetrafenilciclopentadienilo, entilciclopentadienilo, neomentilciclopentadienilo, tetrahydroindenyl, mentiltetrahidroindenilo and neomentiltetrahidroindenilo. Pentamethylcyclopentadienyl is especially preferred. When either of A or B is an amide group represented by -NR ° -, -NHR °, NR 6 ° rR > 9S, v NrRr > 12¿-, -NHR ± or NR j lXlJ "tR_.12 where R9 and R11 are as defined above, and wherein R8 or R12 is an acyl group represented by -C (0) R10 or -C (0) R13, R10 and R13 independently are often a straight or branched chain alkyl of 1 to 7 carbon atoms, aryl or cycloalkyl of 1 to 8 carbon atoms, for example, phenyl Examples of acyl groups that are can represent by R8 or R12 include benzoyl, acetyl, and halogenoacetyl groups, especially the trifluoroacrtyl groups When either of A or B is presented as a sulfonamide group represented by -NR8-, -NHR8, NR8R9, NR12-, NHR12 or NR1 : LR12 wherein R9 and R11 are as defined above, and wherein R8 or R12 is a sulfonyl group represented by -S (O) 2R10-_ or -S (O) 2R13, R10 and R13 independently are often linear or branched chain of 1 to 8 carbon atoms, aryl or cycloalkyl of 1 to 8 carbon atoms, for example phenyl. Preferred sulfonyl groups include methanesulfonyl, trifluoromethanesulfonyl, and especially p-toluenesulfonyl groups. When either of A or B is presented as a group represented by -NR8-, -NHR8, NR8R9, -NR12, -NHR12 or NR R where R and R > n are as already defined, and where RB R12 is a group represented by C (0) NR R, C (S) NR10R14, C (= NR14) SR15, C (= NR14) OR15, C (0) NR13R16, C (S) NR13R16, C (= NR16) SR17, or C (= NR16) OR17, R10 and R13 independently they are often straight or branched chain alkyl of 1 to 8 carbon atoms, such as methyl, ethyl, isopropyl, aryl or cycloalkyl of 1 to 8 carbon atoms, for example "phenyl, and R14-17 are often each independently hydrogen or straight or branched chain alkyl of 1 to 8 carbon atoms, such as methyl, ethyl, isopropyl, aryl or cycloalkyl of 1 to 8 carbon atoms, for example phenyl. It will be recognized that the precise nature of A and B is determined by whether A and / or B are formally bonded to a metal or coordinated to the metal via a single pair of electrons. Groups A and B are connected by a linkage group E. Linkage group E performs an appropriate conformation of A and B in order to allow both, A and B, to bind or coordinate with the metal M. A and B is commonly linked through 2, 3, or 4 atoms. The atoms in the ligament E of A and B may carry one or more substituents. The atoms in E, especially the alpha atoms in A or B, can be linked to A and B, in such a way that a heterocyclic ring, preferably a saturated ring, and particularly a 5, 6 or 7 membered ring is formed. Such a ring can be fused to one or more of the other rings. Often the ligament atoms A and B are carbon atoms. Preferably, one or more of the carbon atoms of ligament A and B carry substituents in addition to A and B. Substituent groups include those which can substitute R1, as defined above. Advantageously, any such substituent groups are selected to be groups which do not coordinate with the metal M. Preferred substituents include the halogen, cyano, nitro, sulfonyl, hydrocarbyl, perhalogenated hydrocarbyl and heterocyclic groups as defined above. The most preferred substituents are alkyl groups of 1 to 6 carbon atoms, and phenyl groups. More preferably, A and B are linked by means of two carbon atoms, and especially an optionally substituted ethyl radical. When A and B are linked by two carbon atoms, the two carbon atoms linking A and B may comprise part of an aliphatic or aromatic cyclic group, particularly a 5, 6 or 7 membered ring. Such a ring may be fused to one or more other such rings. Particularly preferred embodiments are in which E represents a carbon atom separation and one or both of the carbon atoms carries an optionally substituted aryl group as defined above or E represents a separation of 2 carbon atoms which it comprises a cyclohexane ring or cyclopentane, optionally fused to a phenyl ring. Preferably E ~~ comprises part of a compound having at least one stereospecific center. Where any or all of the 2.3 or 4 atoms that bind A and B are substituted in order to define at least one stereospecific center in one or more of these atoms, it is preferred that at least one of the stereospecific centers be located in the adjacent atom of any of groups A or B. When at least one such stereospecific center occurs, it occurs in an enantiomerically purified state. When B represents -O- or -OH and the adjacent atom in E is carbon, it is preferred that B is not part of a carboxyl group. The compounds that can be represented by AEB, or from AEB can be derived by deprotonation, are often aminoalcohols, which include 4-aminoalkanol-oles, l-aminoalkan-4-oles, 3-aminoalkanol-oles, l-aminoalkan-3-ols, and especially 2-aminoalkan-1-ols, l-aminoalkan-2-ols, 3-aminoalkan-2-ols and 2-aminoalkan-3-ols, and particularly 2-amino-ethanols or 3- aminopropanols, or diamines, which include 1,4-dialoalkanes, 1,3-diaminoalkanes, especially 1,2 or 2,3 diaminoalkanes and particularly ethylenediamines. Additional alcohols that can be represented by A-E-B are 2-aminociclopentanoles and 2-aminociclohexanals, preferably fused to a phenyl ring. Additional diamines that can be represented by A-E-B are 1,2-diaminocyclopentanes and 1,2-diaminocyclohexanes, preferably fused to a phenyl ring. Amino groups can advantageously be N-tosylated. When a diamine is represented by A-E-B, preferably at least one group is N-tosylated. The aminoalcohols or diamines are advantageously substituted, especially in the group of ligament, E, by means of at least one alkyl group, such as an alkyl group of 1 to 4 carbon atoms, and particularly a methyl, or at least one aryl group, particularly a phenyl group.

Specific examples of compounds that can be represented by A-E-B and the protonated equivalents from which these can be derived are: H, C Ph Ph Ph Ph Ph Ph H.N OH H, N > - < NH-tcßyi Preferably, the enantiomerically and / or diastereomerically purified forms thereof are used. Examples include (ÍS, 2R) - (+) -norefredine, (IR, 2S) - (+) - cis-l-amino-2-indanol, (ÍS, 2R) -2-amino-l, 2-diphenylethanol , (SS, 2R) - (-) -cis-l-amino-2-indanol, N-tosyl- (1S, 2R) -cis-l-amino-2-indanol, (IR, 2S) - (-) norephedrine, (S) - (+) -2-amino-1-phenylethanol, (1R 2S) -2-amino-1, 2-diphenylethanol, (R) - (-) -2-pyrrolidinemethanol and (S) - ( +) - 2-pyrrolidinemethanol.

The metals that can be represented by M include metals capable of catalyzing hydrogenation by transfer. Preferred metals include the transition metals, more preferably the metals of Group VIII of the Periodic Table, especially ruthenium, rhodium or iridium. When the metal is ruthenium it is preferable that it is present in its valence state II. When the metal is rhodium or iridium it is preferable that they appear in their valence III state. The anionic groups that can be represented by Y include the hydride, hydroxy, hydrocarbyloxy, hydrocarbylamino and halogen groups. When a halogen is represented by Y, preferably the halogen is chlorine. When a hydrocarbyloxy or hydrocarbylamino group is represented by Y, the group can be derived from the deprotonation of the hydrogen donor used in the reaction. The basic ligands that can be represented by-Y include water, alcohols of 1 to 4 carbon atoms, primary or secondary amines of 1 to 8 carbon atoms, or the hydrogen donor that is present in the reaction system. A "preferred basic ligand represented by Y is water.

More preferably, the nature of A-E-B, R7 and Y are chosen so that the catalyst is chiral. When such is the case, it is preferable to employ an enantiomerically and / or diastereomerically purified form. Such catalysts are more advantageously used in asymmetric transfer hydrogenation processes. In many embodiments, the chirality of the catalyst is derived from the nature of A-B. Preferably the process is carried out in the presence of a base, especially when Y is not a vacant site. The pKa of the base is preferably at least 8.0, especially at least 10.0. Conveniently the bases are the alkali metal hydroxides, alkoxides, and carbonates; the tertiary amines and the quaternary ammonium compounds. The preferred bases are sodium 2-propoxide and triethylamine. When the hydrogen donor is not an acid, the amount of base used may be greater than 5.0, commonly greater than 3.0, often greater than 2.5, and especially in the range of 1.0 to 3.5, per moles of catalyst. The substantial excesses of base used by Noyori et al. They seem to be unnecessary. When the hydrogen donor is an acid, the catalyst is preferably connected to a base before the introduction of the hydrogen donor. In such a case, the molar ratio of base of the catalyst before the introduction of the hydrogen donor is often from 1: 1 to 3: 1, and preferably about 1: 1. - Although hydrogen can be present in the gaseous state, the process is normally operated in the absence of hydrogen gas since this seems to be unnecessary. The absence of oxygen is not essential. This has been shown by carrying out the process with a spray of the reaction mixture with pure oxygen: the initial renewal rate is 500h_1 and in two hours at 40% the conversion was obtained. However, better results have been obtained under an inert atmosphere, initial rates of for example 1080h_1 in static nitrogen and 1500 h_1 with nitrogen sprayed. Advantageously, the process is carried out in the substantial absence of carbon dioxide. When the product (s) from the dehydrogenation of the hydrogen donor is volatileFor example, when boiling below 100 ° C, the removal of this volatile product is preferred. The removal can be done by spraying an inert gas. More preferably, the removal is carried out by distillation preferably at a pressure lower than atmospheric. When the reduction pressure distillation is employed, the pressure is often no greater than 500 mmHg, commonly no greater than 200 mmHg, preferably in the range from 5 to 100 mmHg, and more preferably from 10 to 80 mmHg . Suitably the process is carried out at temperatures in the range of less than 78 to above 150 ° C, preferably from less than 20 to more than 110 ° C and more preferably from minus 5 to more than 60 ° C. The initial concentration of the substrate, a compound of formula (1), is appropriate in the range of 0.05 to 1.0 and, for a convenient operation of larger scale, it can be for example greater than 6.0"more especially 0.75 to 2.0 on a molar basis. The molar ratio of the substrate to the catalyst is appropriate in not less than 50: 1 and may be greater than 50000: 1, preferably between 250: 1 and 5000: 1 and more preferably between 500: 1 and 2500: 1. it is preferably used with an excess on the substrate, especially from 5 to 20 folds or, if the convenience permits, greater than, for example, greater than 500 folds.The reaction times are typically in the range from 1.0 minutes to 24 hours, especially above 8 hours and conveniently around 3 hours It seems that by means of the invention substantially shorter times are practicable than those described in the aforementioned publications. In the reaction, the mixing is carried out by standard procedures. A reaction solvent may be present, for example acetonitrile or, conveniently, the hydrogen donor when the hydrogen donor is liquid at the reaction temperature, particularly when the hydrogen donor is a primary or secondary alcohol or a primary or secondary amine . It is usually preferred to operate in the substantial absence of water, but water does not appear to inhibit the reaction. If the hydrogen donor or the reaction solvent is not miscible with water and the desired product is soluble in water, it may be desirable to have water present as a second phase extraction of the product, pushing the balance and preventing the loss of optical purity of the product as the reaction procedure. The concentration of the substrate can be chosen to optimize the reaction time, yield and enantiomeric excess.

In accordance with a second embodiment of the present invention, a catalyst of general formula is provided: wherein: R 'represents an optionally substituted cyclopentadienyl group; A represents -NR8-, NR9-, -NHR8, or NR8R9 wherein R8 is H, C (0) R10, S02R10, C (O) NR10R14, C (S) NR10R14 C (== NR1) SR15, or C ( = NR14) OR15, R v R each independently represents an optionally substituted hydrocarbyl group, perhalogenated hydrocarbyl or an optionally substituted heterocyclic group, and R14 and R15 are each independently hydrogen or a group as defined for R10; B represents -O-, -OH, OR11, -S-, -SH, SR11, -NR11-NR12-, -NHR12, or -NRX1R12 wherein R12 is H, C (0) R13, S02R13, C (0 ) NR13R16, C (S) NR13R16, C (= NR16) SR17 or C (= NR16) OR17, R11 and R13 each independently represents an optionally substituted hydrocarbyl group, a perhalogenated hydrocarbyl or an optionally substituted heterocyclic group, and R16 and R17 are each independently hydrogen or a group as defined for R13; E represents a linkage group; M represents a metal capable of hydrogenation by catalytic transfer; and Y represents an anionic group, a basic ligand or a vacant site; Provided that (i) when Y is not a vacant site at least one of A or B carries a hydrogen atom and (ii) when B represents -O- or -OH, that B is not part of a carboxylate group. In the catalysts according to the present invention, A, E, B, M, R7 and Y can be as described above for the process of hydrogenation by transfer. The species of catalysts that are believed to be substantially as depicted in the above formula. This can be used as an oligomer or a metathesis product, on a solid support or it can be generated in situ.

In certain embodiments it has advantageously been found that certain catalysts preferred in the hydrogenation by transfer of certain types of substrates. The catalysts in which A-E-B is derived from aminoalcohols, particularly norephedrine and cis-aminoindanol, are preferred in the hydrogenation by transfer of aldehydes and ketones to alcohols. Especially, M is also rhodium (III) and R7 represents pentamethylcyclopentadienyl. In addition, it is preferable to use isopropanol as a hydrogen donor and to employ sodium isopropoxide as a base. The catalysts in which A-E-B are derived from N-tosyldiamines are preferred in the hydrogenation reactions by transfer of imines and imino salts. Especially, M is also rhodium (III) and R7 represents pentamethylcyclopentadienyl. In addition, sodium isopropoxide or triethylamine is often used as a base. When the compound of formula (1) is an amine, a mixture of formic acid and triethylamine is preferably used as the hydrogen donor and when the compound of formula (1) is a preformed imino salt, preferably a trifluoroacetate salt , isopropanol is preferably used as the hydrogen donor.

The catalyst can be made by reacting a cyclopentadienyl metal halide complex with a compound of formula AEB as defined above or a pronated equivalent from which it can be derived, and, where, Y represents a vacant site, the reaction of the product of them with a base. The metal cyclopentadienyl halide complex preferably has the formula [MR7Z2] 2 / wherein M and R7 are as defined above, and Z represents a halide, particularly chloride. For the preparation of the catalyst according to the present invention, a solvent is preferably present. The appropriate reaction temperatures are within the range of 0-100, for example 20-70, ° C, which often gives reaction times of 0.5-5.0 hours. After the reaction is completed, the catalyst can be isolated if desired, but it is more convenient to store it as the solution or be used shortly after the preparation. The solution may contain the hydrogen donor and this, if it is a secondary alcohol, it may be present in, or be used as the solvent for, steps (a) and / or (b). The preparation and subsequent handling should preferably be carried out in an inert atmosphere, and particularly in conditions free of carbon dioxide and oxygen. The catalyst or catalyst solution is generally treated with base either before being used in a hydrogenation reaction by transfer, or during its use. This can be done by means of the aggregation of a base to the catalyst in solution, or to the compound of the formula (1) in solution, or by means of the addition to the hydrogenation reaction by transfer. Transfer hydrogenation can be performed by transferring the catalyst solution to the substrate solution, a compound of general formula 1. Alternatively, a substrate solution can be added to the catalyst solution. The base can be added previously to the catalyst solution and / or to the substrate solution, or it can be added later. The hydrogen donor, if not present in the catalytic solution, can be added to the substrate solution, or added to the reaction mixture. The invention is illustrated by means of the following examples.

Unless stated otherwise, the percentages of conversions and percentages of enantiomeric excesses (e.e.) were determined by GC.

EXAMPLE 1 Preparation of the catalyst and reduction of acetophenone Reagent Weight used Weight of moles Molar ratio [Rh (Cp *) Cl2] 2 ** 0.0254g 618.08 1.0 41.2μmol (lS, 2R) - (+) - Norephedrine 0.0209g 151.21 3.36 138.2μmol 2-pr panol (anhydride) lOOml 60.10 31677 1,305μmol KOH 0.1M in 2-propanol 3.3ml 56.11 4.01 0.33mol Acetophenone 2.06g 120.15 209 17mmol Notes: ** Acquired from STREM Chemicals Before the reaction, the solvent is degassed: 100 ml of 2-propanol anhydride was added via syringe to a clean and sealed dry round bottom flask and degassed under vacuum at 20 ° C for 30 minutes. (a) Catalyst Preparation The (+) -norefredine and the rhodium compound are weighed into a clean, dry Schlenk flask. The flask was covered with a "seal-Suba" '(RTM). Their contents were evacuated, then purged at room temperature by means of nitrogen changes. Then (20ml) of 2-propanol was added via cannula. The flask was closed and the flask swirled until the solids began to dissolve. The result was a floating orange and a dark solid. The flask was opened again, a stream of hydrogen was fed, and the contents of the flask were heated to 60 ° C for s hours with 5 minutes. The catalyst was monitored at 30 minute intervals. At each interval there was a dark brown solution, with a black solid at the bottom. (b) Hydrogenation the acetophenone was dissolved in (80 ml) of 2-propanol then degassed for 40 minutes. This solution was added by cannula to the flask containing the catalyst, followed via syringe by the degassed 0.1M solution of KOH in 2-propanol. The mixture was left at room temperature, the samples were taken at intervals and examined by gas chromatography. At the small operation scale the reaction mixture was not sprayed with nitrogen, but the spray must be used for a larger scale production. The results for the production of (R) -1-phenylmethanol are: % conversion - percentage of e.e. 1 h 92 __ 84 The production number, integrated during lh is 189h ~ 1.

EXAMPLE 2 Reagent weight used weight in moles molar ratio [Rh (Cp *) Cl2_2 6.2mg 618.08 1.0 lO.lμmol (lR, 2S) - (+) - cis-l-amino-2-indanol 1.64mg 149.19 1.09molμ acetophenone 2.06g 120.15 1547 17mmol 2-propanol 129974 (a) Catalyst Preparation The rhodium compound and the (IR, 2S) - (+) - cis-2-aminoindanol were suspended in (50 ml) of degassed 2-propanol under a nitrogen atmosphere, heated to 60 ° C and maintained at 60 ° C. C for 1 hour, then cooled to room temperature. The resulting red, orange solution of the catalyst: [(+) - cis- (IR) -amino- (2S) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] - rhodium chloride was passed to the next phase but may be store under an atmosphere of argon or nitrogen. (b) _Hydrogenation The catalytic solution was added to a degassed 0.1M solution of KOH in 2-propanol, followed by a solution of acetophenone in 2-propanol. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours, then treated by neutralization with dilute hydrochloric acid and concentration by vacuum distillation. The residue was diluted with ethyl acetate and washed with an equal volume of aqueous sodium chloride. The organic layer was separated, dried over magnesium sulfate, separated from the solid and freed from the solvent to give __ (1.76g) of crude (S) -1-phenylethanol. Performance of 84%, ee of 89%. The production number, integrated during lh, is 324IT1.

EXAMPLE 3 Reagent weight used weight in moles molar ratio [Rh (Cp *) Cl2] 2 6.3mg 618.08 1.0 10.2μmol (lS, 2R) - (-) - CIS-l-amino-2-indanol 3.1mg 149.19 2.0 20.8μmol acetophenone 1.29g 120.15 1039 10.6mmol 2-propanol 63857 (a) Preparation of the Catalyst The rhodium compound was suspended in 50 ml of 2-propanol and degassed by 3 cycles of vacuum and nitrogen jet. The mixture was heated to moderate reflux until the solid dissolved, then cooled to room temperature. (IR, 2R) - (-) - cis-1-amino-2-indanol was added to the solution with stirring. The mixture was degassed by vacuum cycles and nitrogen jet and heated to 30 ° C for 30 minutes. The resulting red, orange solution of the catalyst: [(-) - cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next phase but may be stored under an atmosphere of argon or nitrogen. (b) hydrogenation Acetophenone was added to the catalyst solution. The mixture was stirred at room temperature for 1 hour. Sodium 2-propoxide (0.25 ml solution of the freshly prepared 0.1M in 2-propanol) was added. The mixture was stirred for 2 hours and samples were taken; 57% of acetophenone has reacted to give (R) -1-phenylethanol of 79% ee. The production number, integrated for 1 hour, is 241h_1. - EXAMPLE 4 _ Reagent weight used weight in moles molar ratio [Go (Cp *) Cl2] 2 ** 7.1 mg 796.71 1.0 8.9μmol (lR, 2S) - (+) - cis-l-amino-2-indanol 1.64mg 149.19 1.23 lμmol acetophenone 2.06 120.15 1908 17mmol 2-propanol 146550 ** Bought from STREM Chemicals. (a) Preparation of the catalyst The iridium compound and the (IR, 2S) - (+) - cis-1-amino-2-indanol were suspended in (50 ml) of degassed 2-propanol under a nitrogen atmosphere, heated to 60 ° C and kept at 60 ° C for 1 hour, then cooled to room temperature. The resulting red, orange solution of the catalyst: [(+) - cis- (IR) -amino- (2S) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -hydrochloride was passed to the next but may be stored under an atmosphere of argon or nitrogen. (b) Hydrogenation The catalyst solution was added to a solution of 0.1M degassed KOH in 2-propanol, followed by a solution of acetophenone in 2-propanol. The mixture was heated to 60 ° C and was stirred at room temperature under a hydrogen atmosphere for 1 hour, then neutralized with dilute hydrochloric acid and concentrated by vacuum distillation. The residue was diluted with ethyl acetate and washed with an equal volume of saturated aqueous sodium chloride. The organic layer was separated, dried over magnesium sulfate, separated from the solid and freed from the solvent to give (0.9g) of crude (S) -1-phenylethanol. Performance of 43%, ee 80%. The production number, integrated during lh, is 410h ~ 1.

EXAMPLE 5 Reagent weight used weight in moles molar ratio [Rh (Cp *) Cl2.2 6.2 mg 618.08 1.0 lOμmol (1S, 2R) -2-amino- 1,2-diphenylethanol 4.3mg 213.28 2.01 20.1μmol tri-ethylamine 7μl 101.19 #imine 53mg 205.26 26 0.26 mmol CF3CO2H 20μl 114.02 0.26 mmol 2-propanol llml 144000 [a) Preparation of the catalyst (LS, 2R) -2-amino-1,2-diphenylethanol (Aldrich: 4.3mg, 20.1μmol) was dissolved in (lOml) of 2-propanol in a small flask with a magnetic stirring jet with nitrogen. The rhodium compound (6.2mg, lOμmol) was added to the solution, along with the triethylamine (7μl). The solution was heated at 60 ° C for 45 minutes during which it turned brown. The resulting solution of the catalyst: [(SS) -amino- (2R) -hydroxydiphenylethyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was used directly in the next reaction. (b) Hydrogenation Imino trifluoroacetate was prepared by the addition of trifluoroacetic acid (20μl, 0.26 mmol) to the imine (53mg, 0.26mmol) in (lml) of 2-propanol. This solution was added to the catalyst solution and heated at 60 ° C for 20 hours. After being quenched in aqueous acid, the aqueous solution was made basic before the extraction of methylene chloride, the product was analyzed by means of? N.m.r. and it was found that 54% of the desired product, the remainder is the imine starting material.

EXAMPLE 6 Reagent weight used weight in moles molar ratio [Rh (Cp *) Cl2] 2 6.2mg 618.08 1.0 9.73μmol N-tosyl- (IS, 2R) -cis-l-amino-2-indanol 6.8mg 303.38 2.3 22.4μmol 2-propanol Iml triethylamine 7μl 101.19 Imine 40mg 205.26 0.195mmol CF3CO2H 15μl 0.195mmol (a) .Preparation of the catalyst N-Tosyl- (SS, 2R) -cis-l-amino-2-indanol (6.8mg, 22.4μmol) was dissolved in (Iml) of 2-propanol in a small nitrogen-blasted jar with magnetic stirring. The rhodium compound (6.2mg, 9.73μmol) was added to the solution, which was then heated to 60 ° C per lh. Triethylamine (7μmol) was added. The solution changed color from orange to purple. The solution was maintained at 60 ° C for another 20 minutes, then cooled to room temperature. The resulting solution of the catalyst: [N-tssyl-cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was stored under a nitrogen atmosphere. (b) Hydrogenation Imino trifluoroacetate was prepared by the addition of (15μl, 0195mmol) of trifluoroacetic acid to the imine (40mg, 0.195mmol) in (lml) of 2-propanol. The catalyst solution was added to the mixture heated at 60 ° C for 16 hours. After that which was quenched in aqueous sodium bicarbonate and extraction in methyl chloride, the product was analyzed by ^ n. .r. and 42% of the desired product is found: the remainder was the imine of the starting material.

EXAMPLE 7 Reagent weight used weight in moles molar ratio [Rh (Cp *) Cl2] 2 6.3 g 618.08 1.0 10.2μmol N-tosyl- (IR, 2R) -1, 2-diphenylethylene diamine 7.3mg 366.48 1.93 20μmol Triethylamine 6μl 101.19 4.18 43μmol 2-propanol lOml 60.1 CH3CN 6.4ml 41.05 #Item 109mg 205.26 0.53mmol triethylamine / formic acid 2: 5 0.25ml (a) Catalyst Preparation N-tosyl- (IR, 2R) -1,2-diphenylethylenediamine (7.3mg, 20μmol) and the rhodium compound (6.3mg, 10.2μmol) in (lOml) of 2-propanol were suspended in a small flask blasted with nitrogen. Triethylamine (6μl) was added. The mixture was stirred at 55 ° C until all solids dissolved and then heated at 80 ° C for 30 minutes then cooled to room temperature. The resulting solution of the catalyst: [N-tosyl- (IR) -amino- (2R) -aminodiphenylethyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was stored under a nitrogen atmosphere. _ (b) hydrogenation [Substrate: Catalyst Ratio 266: 1] A portion of (8ml) of the above catalytic solution was placed in a flask and the solvent was evaporated by the vacuum application. The residue was redissolved in (6.4 ml) of acetonitrile and degassed with nitrogen. A nitrogen-purged flask 7 was charged with the imine (109 mg, 0.53 mmol) and 0.8 ml of the catalytic solution followed by (0.25 ml) of a 2: 5 mixture of formic acid and triethylamine. The mixture was heated at 60 ° C for 1 hour, quenched by the addition of water and then extracted into methylene chloride, dried over magnesium sulfate and the crude product was analyzed by 1 HNMR which showed to be > 95% of the desired amine. Change of chiral 1Hn.m.r. which showed that the amine is 74.8% ee.

EXAMPLE 8 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 6mg 618.08 1.0 9.7μmol (1S, 2R) - (-) - CIS-1-amino-2-indanol 3 .2mg 149. 19 2.1 22.1μmol acetophenone 0. 126g 120 15 lmmol 2-butanol 20ml 74. 12 0.22mol (a) Preparation of the catalyst The rhodium compound and (ÍS, 2R) - (-) - cis-1-amino-2-indanol were suspended in degassed 2-butanol (20ml) under a nitrogen atmosphere, and the reaction was purged with nitrogen by 30 minutes. The yellow mixture was heated at 35 ° C for 0.5 hour, during which time the color was intensified to red / orange, then cooled to room temperature. The resulting red / orange catalyst solution: [(-) - cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next phase but may be stored under an atmosphere of argon or nitrogen. (b) Hydrogenation [Substrate: Proportion of catalyst 539: 1] (0.126g, lmmol) of acetophenone was added to a dry flask. Then a portion of (2ml) of the catalytic solution was added followed by a solution of (25μl of 0.2M solution in 2-propanol) of 2-propoxide sodium. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. This gave (R) -1-phenylethanol. Yield of 66.2%, ee 87%. The initial production number, integrated for 1 hour, is 574h "1.

EXAMPLE 9 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 6.1mg 618.08 1.0 9.9μmol (lS, 2R) - (-) - cis-l-amino-2-indanol 3mg 149.19 2.03 20μmol acetophenone 1.089g 120.15 9. lmmol 2-butanol 20ml 74.12 0.22mol (a) Preparation of the catalyst The rhodium compound and (ÍS, 2R) - (-) - cis-1-amino-2-indanol were suspended in degassed 2-butanol (20ml) under a nitrogen atmosphere, and the reaction was purged with nitrogen by 30 minutes. The yellow mixture was heated at 35 ° C for 20 minutes, during which time the color was intensified to red / orange, then cooled to room temperature. The resulting red, orange solution of the catalyst: [(-) - cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next phase but may be stored under an atmosphere of argon or nitrogen. (b) Hydrogenation [substrate: Catalyst Ratio 460: 1] 0.45ml of 0.2M solution in 2-propanol) of sodium 2-propoxide was charged to the catalytic solution. After 2 minutes, acetophenone (1.0889, 9.1 mmol) was added. The mixture was stirred under vacuum at 35 ° C for 1.5 hours, then heated to maintain a temperature between 40-45 ° C for 4 hours. This gives (R) -1-phenylethanol.

Yield of 87.1%, ee 87%. The production number, integrated during lh, is 1502h ~ 1.

EXAMPLE 10 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 5.9mg 618.08 1.0 9.57μmol (l_S, 2R) - (-) - cis-l-amino-2-indanol 3. lmg 149.19 2.17 20.8μmol a-tetralone 0.5ml 146.19 393 3.76mmol 2-propanol 50ml 60.1 0.653mmol (a) Preparation of the catalyst The rhodium compound and the (ÍS, 2R) - (-) - cis-1-amino-2-indanol were suspended in (50 ml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen by 30 minutes. The mixture was heated at 35 ° C for 10 minutes. The resulting orange solution of the catalyst: [(-) - cis- (1S) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next stage but may be stored under a argon or nitrogen atmosphere.

(B) Hydrogenation The catalytic solution (0.38ml of 0.1M 2-propanol solution) of 2-propoxide sodium was charged followed by (0.5ml, 3.76mmol) of a-tetralone. The mixture was stirred under vacuum (80mmHg) at 35 ° C for 2 hours, after the first hour the flask was again filled with nitrogen and enough charged 2-propanol to compensate for the volume removed by distillation. This gives (R) -1-tetralol. Yield of 98.4%, 95.7% ee. The production number, integrated for 1 hour, is 185h_1.

EXAMPLE 11 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 24.4mg 618.08 1.0 39.48μmol (lR, 2S) - (-) - norephedrine 12.1mg 151.21 2.03 80μmol a-tetralone 5ml 146.19 952 37.6μmol 2-propanol 125ml _ 60.1 1.63mol (a) Catalyst Preparation The rhodium compound and the (IR, 2S) - (-) - norephedrine were suspended in (75ml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen for 30 minutes. The mixture was heated at 35 ° C for 30 minutes. The resulting orange solution of the catalyst: [(-) - (IR, 2S) -norefedrinil] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next phase but may be stored under an argon or nitrogen atmosphere . (b) Hydrogenation The (1 mL of 0.1M solution in 2-propanol) of sodium 2-propoxide was charged to the catalytic solution and the pressure reduced (40-80mmHg). The a-tetralone (5ml, 37.6mmol) in (75ml) of 2-propanol was then added over a period of 15 minutes. The mixture was stirred under vacuum (40-80mmHg) at 35 ° C for 4 hours, at intervals the flask was refilled with nitrogen and enough charged 2-propanol to compensate for the volume removed by the liquid. distillation. This gives (S) -1-tetralol. Yield of 96%, ee 96.2%. The production number, integrated for 1 hour, is 382 h "1.

EXAMPLE 12 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 26.4mg 618.08 1.0 42.7μmol (lS, 2R) - (-) - cis l-amino-2-indanol 13.4mg 149.19 2.1 89.8μmol acetophenone 5ml 120.15 42.9mmol 2-propanol 270ml (a) Preparation of the Catalyst The rhodium compound and the (ÍS, 2R) - (-) - cis-1-amino-2-indanol were suspended in (20 ml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen for 30 minutes. The mixture was heated at 40-50 ° C for 30 minutes, during which time the color was intensified to deep red, then cooled to room temperature. The resulting red solution of the catalyst: [(-) - cis- (1S) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] rhodium chloride is passed to the next phase but may be stored under one atmosphere of argon or nitrogen. (b) Hydrogenation [Substrate: Proportion of Catalyst 5018: 1] (5 ml, 42.9 mmol) of acetophenone was added to a dry Schlenck flask containing 250 ml of 2-propanol. Then one was added a portion of (2ml) of catalytic solution followed by the 2-propoxide sodium solution (0.3ml of 1M solution of 2-propanol). The mixture was stirred at 18 ° C under vacuum (28mmHg) for 5 hours. This gives (R) -1-phenylethanol. Yield of 74%, ee 86.8%. The initial production number, integrated for 1 hour, is 1947h " EXAMPLE 13 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 6.2mg 618.08 1.0 lOμmol (lS, 2R) - (-) - cis-l-amino-2-indanol 4.3mg 149.19 2.88 28.8μmol p-methylace -Tophenone 0.280g 134.18 2. lmmol 2-propanol (a) Preparation of the catalyst The rhodium compound and the (ÍS, 2R) - (-) - cis-l-amino-2-indanol were suspended in (lOml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen by 30 minutes. The mixture was heated at 90 ° C for 20 minutes, during which time it was intensified to red / orange, then cooled to room temperature. The resulting red, orange catalyst solution: [(-) - cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu5)] - pentamethylcyclopentadienyl] -rhodium chloride was passed to the next stage but may be store under an atmosphere of argon or nitrogen. (b) Hydrogenation [Substrate: Proportion of Catalyst 523: 1] Added (0.28g, 2. lmmol) of p-methylacetophenone to a dry flask. Then a portion of (2ml) of the catalytic solution was added followed by the sodium 2-propoxide solution (90μl of 0.1M 2-propanol solution).

The mixture was stirred at room temperature under nitrogen for 2 hours. This gives 1- (p-methylphenyl) ethanol. Yield 56.8%, ee 56%. The production number, integrated for 1 hour, is 1064h-1.

EXAMPLE 14 - Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 6.2mg 618.08 1.0 lOμmol (lS, 2R) - (-) - cis-l-amino-2-indanol 4.3mg 149.19 2.88 28.8μmol p-trifluoromethyl-acetophenone 0.384g 188.15 2mmol 2- propanol (a) Preparation of the catalyst The rhodium compound and the (ÍS, 2R) - (-) - cis-1-amino-2-indanol were suspended in (lOml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen by 30 minutes. The mixture was heated at 90 ° C for 20 minutes, at which time the color was intensified to red / orange, then cooled to room temperature. The resulting red, orange catalyst solution: [(-) - cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next stage but may be stored in an atmosphere of argon or nitrogen. (b) Hydrogenation [Substrate: Proportion of catalyst 498: 1] Add (0.384g, 2mmol) of p-trifluoromethylacetophenone to a dry flask. Then a portion of (2ml) of catalytic solution was added followed by (90μl of 0.1M solution in 2-propanol) of the sodium 2-prop'oxide solution. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. This gives 1- (p-trifluoromethylphenyl) ethanol. Yield of 96.7%, ee 73.8%. The initial production number, integrated for 1 hour, is 412h-1.

EXAMPLE 15 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 6.2mg 618.08 1.0 lOμmol (lS, 2R) - (-) - cis-l-amino-2-indanol 3.3mg 149.19 2.2 22.1μmol p-chloroacet-tofeñona 0.162g 154.6 517 1.05mmol 2-propanol (a) Catalyst Preparation The rhodium compound and the (IS, 2R) - (-) - cis-1-amino-2-indanol were suspended in (lOml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen for 30 minutes. The mixture was heated at 90 ° C for 20 minutes, during which time the color intensified to red / orange, then cooled to room temperature. The resulting red, orange catalyst solution: [(-) - cis- (IS) -amino- (2R) -hydroxyindanyl] - [(mu 5) -pentamethylcyclopentadienyl] -thio rhodium chloride is passed to the next stage but may be Store in a nitrogen or argon atmosphere. (b) Hydrogenation [Substrate: Catalyst Ratio 524: 1] _ (0.162g, 1.05mmol) of p-chloroacetophenone was added to a dry flask. Then a portion of (2ml) of catalytic solution was added followed by a solution of (50μl of 0.1M solution in 2-propanol) of sodium 2-propoxide. The mixture was stirred at room temperature under a nitrogen atmosphere for 19 hours.This gives 1- (p-chlorophenyl) ethanol 90.6% yield, 71.6% ee.The initial production number, integrated over 1 hour, is 846h-1.

EXAMPLE 16 Reagent Weight used Weight in moles Molar ratio [R? T (Cp *) Cl2] 2 6.2mg 618.08 1.0 lOμmol (lS, 2R) - (-) - cis-l-amino-2-indanol 3.3mg 149.19 2.2 22.1μmol o-chloroacetofenone 0.160g 154.6 lmmol 2-propanol a) Preparation of the Catalyst The rhodium compound and the (ÍS, 2R) - (-) - cis-1-amino-2-indanol were suspended in (lOml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen by 30 minutes. The mixture was heated at 90 ° C for 20 minutes, during which time the color was intensified to red / orange, then cooled to room temperature. The resulting red, orange catalyst solution: [(-) - cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next stage but may be stored in an atmosphere of nitrogen or argon. b) Hydrogenation [Substrate: Catalyst Ratio 517: 1] O-Chloroacetophenone (0.16g, lmmol) was added to a dry flask. Then a portion of (2ml) of catalytic solution was added followed by a solution of (50μl of O.lM solution in 2-propanol) of 2-propoxide sodium. The mixture was stirred at room temperature under a nitrogen atmosphere for 19 hours. This gives 1- (o-chlorophenyl) ethanol.

Yield of 94.3%, ee 69.1%. The initial production number, integrated for 1 hour, is 1951T1.

EXAMPLE 17 Reagent Weight used Weight in moles Molar ratio [Go (Cp *) Cl2_ 2 32. 8mg 796. 67 1. 0 41 .2μmol (lS, 2R) - (+) -norefedrine 20mg 151.21 3.2 132μmol acetophenone 2ml 120.15 413 17mmol 2-propanol lOOml a) Preparation of the Catalyst The iridium compound and (+) - norephedrine were suspended in (20 ml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen for 30 minutes. The mixture was heated at 60 ° C for 90 minutes, then cooled to room temperature. The resulting catalyst solution: [(+) - (IS, 2R) -norefedrinyl] - [(mu 5) -pentamethylcyclopentadienyl] -hydrochloride was passed on to the next phase but may be stored under a nitrogen or argon atmosphere. b) Hydrogenation They were dissolved (2ml, 17mmol) of acetophenone in (80ml) of 2-propanol and purged with nitrogen. Then the catalytic solution was added followed by a solution of (3.3ml of O.lM solution in 2-propanol) of potassium hydroxide. The mixture was stirred at room temperature under a nitrogen atmosphere for 10 hours. This gives 1-phenylethanol. Yield of 68%, ee 49%. The initial production number, integrated for 1 hour, is 318h -i EXAMPLE 18 Reagent Weight used Weight ei Molar ratio [Rh (Cp *) Cl2] 2 ig 618.08 1.0 1.62mmol (lS, 2R) - (-) - cis-l-amino-2-indanol 0.5mg 149.19 2.08 3.36mol tetralone 200ml 146.19 928 1.5mol 2-propanol 101 (a) catalyst preparation Charge (9.51) of 2-propanol to reaction flask 201 which was freed of oxygen and refilled with nitrogen. The rhodium compound (lS, 2R) - (-) - cis-2-aminoindanol was charged to the vessel with stirring and the mixture was freed of oxygen and refilled with nitrogen. The orange suspension was heated to 35 ° C until a clear red solution of the catalyst formed: [(-) - cis- (SS) -amino- (2R) -hydroxyindanyl] - [(mu 5) -pentamethylcyclopentadienyl] -chloride rhodium. (b) hydrogenation Tetralone (200ml, 1.5mol) was charged to the catalytic solution, followed by (0.51) of 2-propanol. The pressure was reduced to (28.5mmHg) and then a solution of (120ml of O.lM solution in 2-propanol) of 2-sodium propoxide was charged. The mixture was stirred at room temperature and sufficient charged 2-propanol to compensate for the volume removed by distillation. This gives (R) -l-tetralol. Yield of 96.9%, ee 86.9%. The production number, integrated during Ih, is 358h-1.

EXAMPLE 19 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 lg 618.08 1.0 1.62mmol (lS, 2R) - (-) - cis-l-amino-2-indanol 0.49g 149.19 2.04 3.31mol acetophenone 179g 120.15 920 1.49mol 2-propanol 101 (a) Preparation of the catalyst The 2-propanol (9.51) was charged to a reaction bottle 201 which was freed of oxygen and refilled with nitrogen. The rhodium compound and the (1S, 2R) - (-) - cis-l-amino-2-indanol were charged to the vessel with stirring and the mixture was freed from oxygen and refilled with nitrogen. The mixture was heated to 35 ° C until a red catalyst solution formed: [(-) - cis- (1S) -amino- (2R) -hydroxyindanyl] - [(mu5) -pentamethylcyclopentadienyl] rhodium chloride. (b) Hydrogenation The catalyst solution was charged (200ml, 1.5mol), followed by (0.51) 2-propanol. The pressure was reduced to (28.5mmHg) and then a solution of (120ml of O.lM solution of 2-propanol) 2-propanol. The mixture was stirred at room temperature under a nitrogen atmosphere for 2.5 hours, at hour intervals the flask was refilled with sufficient charged 2-propanol to compensate for the volume removed by distillation. Is all (R) -1-phenylethanol. Yield 99.6%, ee 82.9%. The production number, integrated for 1 hour, is 454h-1.

EXAMPLE 20 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 6.3g 618.08 1.0 lOμmol (lS, 2R) - (-) - 2-amino-l, 2-dimethylethanol 4.5mg 213.28 2.07 21.1μmol acetophenone 0.120g 120.15 490 0.99mmol 2-propanol (a ) Catalyst Preparation The rhodium compound and the (IR, 2S) - (-) -2-amino-1,2-diphenylethanol were suspended in (20 ml) of 2-propanol under a nitrogen atmosphere, and then the reaction was purged with nitrogen by 30 minutes. The mixture was heated at 80 ° C for 30 minutes, then cooled to room temperature. The resulting catalyst solution: [(-) - (2S) -amino- (IR) -hydroxydiphenylethyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next stage but may be stored under an atmosphere of argon or nitrogen (b) hydrogenation Added (0.12g, 0.99mmol) acetophenone to a dry flask. Then a portion of (2ml) of catalytic solution was added followed by a solution of (50μl of O.lM of a solution of 2-propanol) of 2-propoxide sodium. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. This gives 1-phenylethanol Yield of 90.7%, ee 66%. The production number, integrated for 1 hour, is 82ßh "1.

EXAMPLE 21 Reagent Weight used Weight in moles Molar ratio [Rh (Cp *) Cl2] 2 6.2mg 618.08 1.0 10.4μmol (S) - (+) -2-amino-1-phenylethanol 2.7mg 137.18 1.96 19.7μmol acetophenone 0.140g 120.15 1.17mmol 2-propanol (a) Preparation of the catalyst The rhodium compound and the (S) - (+) - 2-amino-1-phenylethanol were suspended in (20 ml) of degassed 2-propanol under a nitrogen atmosphere, and the reaction was purged with nitrogen for 30 minutes. The mixture was heated at 80 ° C for 30 minutes, then cooled to room temperature. The resulting solution of the catalyst: [(+) - (2) -amino- (SS) -hydroxyphenylethyl] - [(mu5) -pentamethylcyclopentadienyl] -rhodium chloride was passed to the next stage but may be stored under an argon atmosphere or nitrogen. (b) Hydrogenation [Substrate: Proportion of the catalyst 580: 1] Added (0.14g, 1.17mmol) to a dry flask. Then a portion of (2ml) of catalytic solution was added followed by a solution of (50μl of O.lM solution in 2-propanol) of sodium 2-propoxide. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. This gives 1-phenylethanol. Yield of 62.4%, ee 77.4%. The initial production number, integrated for 1 hour, is 487h_1.

It is noted that in relation to this date, the best method known to the applicant, to put into practice the aforementioned invention is that it is clear from the manufacture of the objects to which it refers. Having described the invention as above, property is claimed as contained in the following:

Claims (24)

1. A process for transfer hydrogenation of a compound of formula (1) to produce a compound of formula (2); (D (2) wherein X represents CR3R4, NR5, (NR5R6) + Q ", O or S; RX, R2, R3, R4, R5, and R6 each independently represents a hydrogen atom, an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or a optionally substituted heterocyclic group, one or more of R1 &R2, R1 &R3, R2 &R4, R3 &R4, R1 &R5, R2 &R6, and R5 &R6 optionally are ligated in such a manner which form (s) an optionally substituted ring (s), and Q ~ represents an anion, said process comprises the reaction of the compound of formula (1) with a hydrogen donor in the presence of a catalyst; characterized in that the catalyst has the general formula: .AND. A. ß M Y 'V Wherein: R7 represents an optionally substituted cyclopentadienyl group; A represents -NR8-, NR9, -NHR8 or NR8R9 wherein R8 is H, C (0) R10, S02R > 10, C (S) NRl ± O? NRliß-, C (= NR1) OR15, R9 and R10 each independently represents an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclic group, and R14 and R15 are each one independently hydrogen or a group as defined for R10; B represents -O-, -OH, OR11, -SS, -SH, SR11, -NR11-, -NR12, NHR12 or -NR ^ R12 wherein R12 is H, C (0) R13, S02R13, C (0) NR > 1i3OtR-, 1 ± 6β, C (S) NR > 1x3-3tR, 1J-6 °, C (= NR, 16t3,) SR17 or C (= NR16) OR17, R11 and R13 each independently represents an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclic group, and R16 and R17 are each independently hydrogen or a group as defined for R13; E represents a linkage group; M represents a metal capable of hydrogenation by catalytic transfer; and Y represents an anionic group, a basic ligand or a vacant site; Provided that when Y is not a vacant site at least one of A or B carries a hydrogen atom.

2. A process according to claim 1, characterized in that the compound of formula (1) is a ketone, an imine or an imino salt.

3. A process according to any of claims 1 or 2, characterized in that M is a transition metal of group VIII, especially ruthenium, rhodium or iridium.

4. A process according to any of claims 1 to 3, characterized in that R7 is a cyclopentadienyl group substituted with between 3 and 5 substituents, preferably 5 substituents, especially a pentamethylcyclopentadienyl group.

5. A process according to any of claims 1 to 4, characterized in that AEB is, or is derived from, an aminoalcohol or a diamine, preferably selected from an optionally substituted 2-aminoethanol, an optionally substituted 3-aminopropanol and an ethylenediamine. "optionally replaced.

6. A process according to claim 5, characterized in that any of A or B carries an acyl or sulfonyl group, preferably an enosulfonyl tol, methanesulfonyl, trifluoromethanesulfonyl or an acetyl group.

7. A process according to claim 5, characterized in that A-E-B is, or is derived from, one of the following: í¡? HO N! H. HO > -N

8. A process according to any of the preceding claims, characterized in that the compound of formula (1) is prochiral and the catalyst is chiral, an enantiomeric and / or diastereomerically purified form of the catalyst that is employed, wherein the compound of formula (1) ) is dehydrogenated asymmetrically.

9. A process according to claim 8, characterized in that A-E-B comprises at least one stereospecific center.

10. A process of conformity according to any of claims 1 to 9, characterized in that the hydrogen donor is selected from hydrogen, primary and secondary alcohols, primary and secondary amines, carboxylic acids and their esters and amine salts, easily dehydrogenatable hydrocarbons, clean reduction agents, and any combination thereof.

11. A process according to claim 10, characterized in that the hydrogen donor is propan-2-ol, butan-2-ol or a mixture of triethylamine and formic acid.

12. A process according to any of claims 1 to 11, characterized in that the products from the dehydrogenation of the hydrogen donor are removed by means of vacuum distillation.

13. A process according to any of claims 1 to 2, characterized in that a ketone of formula (1) is dehydrogenated by transfer in the presence of a catalyst in which A-E-B is, or is derived from, an aminoalcohol.

14. A process according to claims 1 to 12, characterized in that an imine or an imino salt of formula (1) is dehydrogenated by transfer in the presence of a catalyst in which AEB is, or is derived from, an N-tosyldiamine .

15. A process according to any of the preceding claims, characterized in that the process is carried out in the presence of a base having a pKa of at least 8.0.

16. A catalyst of general formula: M Y 'V wherein: R7 represents an optionally substituted cyclopentadienyl group; A represents -NR8-, -NR9-, -NHR8 or -NR8R9 wherein R8 is H, C (0) R10, S02R10, C (O) NR10R14, C (S) NR10R14, C (= NR14) SR15 or C (= NR14) OR15, R9 and R10 each independently represents an optionally substituted hydrocarbyl group, a perhalogenated hydrocarbyl or an optionally substituted heterocyclic group, and R14 and R15 are each independently hydrogen or a group as defined for R10; B represents -O-, -OH, OR11, -S-, -SH, SR11, -NR11-, -NR12-, -NHR 12 -NR XRX in (0) R 13, S02R, 13 C (0) NR13R16, C (S) NR13R16, OR > 1x7 /, R > nxx and _R 13 each independently represents an optionally substituted hydrocarbyl group, perhalogenated hydrocarbyl or an optionally substituted heterocyclic group, and R 16 and R 17 are each independently hydrogen or a group as defined for R 13; E represents a ligament group; M represents a metal capable of catalyzing a hydrogenation by transfer; and Y represents an anionic group, a basic ligand or a vacant site; provided that (i) when Y is not a vacant site that at least one of A or B carries a hydrogen atom and (ii) when B represents -O- or -OH, that B is not part of a carboxylate group.

17. A catalyst according to claim 16, characterized in that M is a transition metal of group VIII, especially ruthenium, rhodium or iridium.

18. A catalyst according to any of claims 16 or 17, characterized in that R7 is a cyclopentadienyl group substituted with between 3 and 5 substituents, preferably 5 substituents, and especially a pentamethylcyclopentadienyl group.

19. A catalyst according to any of claims 16 to 18, characterized in that A-E-B is derived from an aminoalcohol or a diamine, preferably an optionally substituted 2-aminoethanol, an optionally substituted 3-aminopropanol or an optionally substituted ethylenediamine.

20, A catalyst according to claim 19, characterized in that one of the two or both A or B, when an amino group, carries an acyl or sulfonyl group, preferably a toluenesulfonyl, • methanesulfonyl, trifluoromethanesulfonyl or an acetyl group, especially a trifluoroacetyl or a p-toluenesulfonyl group.

21. A catalyst according to claim 19, characterized in that A-E-B is, or is derived from, one of the following:

22. A catalyst according to any of claims 16 to 21, characterized in that the catalyst is chiral, and resolves forms of the same.

A catalyst according to claim 22, characterized in that A-E-B comprises at least one stereospecific center.

24. A process for the preparation of a catalyst according to any of claims 16 to 23, characterized in that it comprises the reaction of a cyclopentadienyl metal halide complex with a compound of formula A-E-B or a pronated equivalent from which it can be derived.