MXPA01003163A - Transfer hydrogenation process - Google Patents

Abstract

A catalytic transfer hydrogenation process is provided. The catalyst employed in the process is a metal neutral hydrocarbyl 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 mixture of triethylamine and formic acid. The process can be employed to transfer hydrogenate iminium salts, which are preferably prochiral.

Description

PROCESS OF HYDROGENATION BY TRANSFER This invention relates to hydrogenation by catalytic transfer, particularly in the presence of a complexed transition metal and to a process for the preparation of optically active compounds.

According to a first aspect of the present invention, there is provided a process for the hydrogenation by transfer of a compound of the formula (1) (D where : X represents (NR3R4) + Q ", N + R5-0 ~, (NR6OR7) + Q", (NR8NR9R10) + Q ", (NR8NR9C (= NRn) R12) + Q", (NR8NR9S02R13) + Q ', or (NR8NR9COR14) + Q-; Q "represents a monovalent anion; R \, RJ, R R5, R6, R7, R8, R9, R10, and R11 each REF. DO NOT. 127864 independently represents a hydrogen atom, an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group, or more of R1 & R2, R1 & R3, R2 & R4, R3 & R4, R1 & R5, R1 & R6, R2 & R7, R1 & R8, R1 & R9, R6 & R7, R8 & R9 and R9 & R10 which are optionally linked in such a manner to form an optionally substituted ring or rings; Y R12, R13 and R14 each independently represent an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group; the process comprises reacting the compound of the formula (1) with a hydrogen donor in the presence of a catalyst, characterized in that the catalyst has the general formula: , B * - 15 AND R wherein R 15 represents an optionally substituted hydrocarbyl or perhalogenated hydrocarbyl ligand; A represents -NR16-, -NR17-, -NHR16, -NR16R17 or -NR17R18 wherein R16 is H, C (0) R18, S02R18, C (0) NR18R22, C (S) NR18R22, C (= NR22) SR23 or C (= NR22) OR23, R17 and R18 each independently represents an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl or an optionally substituted erocyclyl group and R22 and R23 are each independently hydrogen or a group as defined for R18; B represents -O-, OH, OR19, -S-, -SH, SR19, -NR19-, -NR20-, NHR20-, -NR19R20, -NR19R21, -PR19- or -PR1 R21 wherein R20 is H, C (0) R21, S02R21, C (0) NR21R24, C (S) NR21R24, C (= NR2) SR25 or C (= NR24) OR25, R19 and R21 each independently represent a substituted hydrocarbyl, perhalogenated hydrocarbyl or a heterocyclyl group optionally substituted, and R24 and R25 are each independently hydrogen or a group as defined for R21; E represents a linking group; M represents a metal capable of catalyzing hydrogenation by transfer; and Y represents an anionic group, a basic ligand or a vacant site; with the proviso that when Y is not a vacant site that is at least of A or B that carries a hydrogen atom.

The catalytic species are believed to be substantially as represented in the above formula. It could be introduced in a solid support.

When X represents (NR3R4) + Q ~, the compounds of the formula (1) are iminium salts. Preferred iminium salts include protonated iminium salts and quaternary imine salts, preferably quaternary imine salts. The quaternary imine salts are represented by the compounds of the formula (I) in which R3 and R4 are not hydrogen.

Anions that could be represented by Q "include optionally substituted halides, arylsulphates, such as optionally substituted phenyl, and naphthyl sulfonates, optionally substituted alkylsulphates including halogenated alkylsulfonates, such as alkylsulfonates < r1.20, optionally substituted carboxylates, such as C1_10 alkyl and aryl carboxylates, ions derived from the polyhalogenation of boron, phosphorus or antimony and other common inorganic ions, for example perchlorate Examples of anions that could be present are bromide, chloride, iodide, hydrogen sulfate, tosylate, format, acetate, tetrafluoroborate, hexafluorophosphate, hexafluoro anion, perchlorate, trifluoromethanesulfonate and trifluoroacetate - Preferred anions include bromide, chloride, iodide, formate and trifluoroacetate, particularly preferred anions include iodide, formate and trifluoroacetate.

The hydrocarbyl groups that could be represented by R 1"14, R 17, R 18, R 19 and R 21" 25 independently include alkyl, alkenyl and aryl groups and any combination thereof, such as aralkyl and alkaryl, for example benzyl groups.

Alkyl groups that could be represented by R1"14, R17, R18, R19 and R21'25 include linear or branched alkyl groups comprising up to 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 could be cyclic, commonly comprising from 3 to 10 carbon atoms. carbon in the longer ring and optionally characterizing one or more bridging rings Examples of the alkyl groups that could be represented by R 1"14, R 17, R 18, R 19 and R 21 ~ 25 include methyl, ethyl, propyl, 2-propyl groups , butyl, 2-butyl, t-butyl and cyclohexyl.

The alkenyl groups that could be represented by R 1"14, R 17, R 18, R 19 and R 21" 25 include C2.20 alkenyl groups and preferably C2_6 alkenyl. One or more carbon-carbon double bonds may be present. The alkenyl group could carry one or more substituents, particularly phenyl substituents. Examples of the alkenyl groups include vinyl, styryl and indenyl groups. When either R 1 or R 2 represent an alkenyl group, a carbon-carbon double bond is preferably located in the β-position with respect to the radical C = X. When R1 or R2 represent an alkenyl group, the compound of the formula (1) is preferably a imino, β-unsaturated compound.

The aryl groups that could be represented by R1"14, R17, R18, R19 and R21" 25 could contain 1 ring or 2 or more fused rings, which could include cycloalkyl, aryl or heterocyclic rings. Examples of aryl groups that could be represented by R.sup.1", R.sup.17, R.sup.18, R.sup.19 and R.sup.2I-2S include phenyl, tolyl, f.sub.1 or p.sub.r or f.sub.1 nyl groups, chlorophenyl, bromophenyl, trifluoromethylphenyl, anisyl, naphthyl and ferrocenyl.

The perhalogenated hydrocarbyl groups that could be represented by R 1"14, R 17, R 18, R 19 and R 21" 25 independently include perhalogenated alkyl and aryl groups and any combination thereof, such as aralkyl and alkaryl groups. Examples of the perhalogenated alkyl groups that could be represented by R1"14, R17, R18, R19 and R21" include -CF3 and -C2F5-.

Heterocyclic groups that could be represented by R1-14, R17, R18, R19 and R21"25 independently include aromatic, saturated and partially unsaturated ring systems and could constitute 1 ring or 2 or more fused rings which could include cycloalkyl, aryl or heterocyclic group The heterocyclic group will contain at least one heterocyclic ring, the longest of which will commonly comprise from 3 to 7 ring atoms, wherein at least one atom is carbon and at least one atom is any of 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 the heterocyclic groups that could be represented by R1"14, R17, R18, R19 and R21"25 include pyridyl, pyrimidyl, pyrrolyl, thiophenyl, furanyl, indolyl, quinolyl, isoquinolyl, imidazoyl and triazoyl groups.

When any of R1"14, R17, R18, R19, and R21-25 is a heterocyclic or substituted hydrocarbyl group, the substituents should be such as not to adversely affect the speed or reaction of the reaction, optional substituents include halogen, cyano, nitro, hydroxy, amino, thiol, acyl, hydrocarbyl, hydrocarbyl perhaloge ao, heterocyclyl, hydrocarbyloxy, mono or di-hydrocarbylamino, hydrocarbyl, esters, carbonates, amides, sulfonyl and sulfonamido 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, R1 & R6, R2 & R7, R1 & R8, R1 & R9, R6 & R7, R8 & R9 and R9 & R10 are linked in such a way that when taken together with the carbon atom and / or the X atom of the compound of the formula (1) that a ring is formed, it is preferred that these be 5, 6 or 7 membered rings. The rings formed in this way could be further fused with one another to other ring systems. Examples of rings that could be formed in this way include wherein X is as defined above and the rings could be optionally substituted or they could be fused to other rings.

In certain preferred embodiments, R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, R 11, R 12, R 13 and R 14 are all independently alkyl x 6 or are a combination of aryl, particularly phenyl, C 1,6 alkyl and C6_10 aralkyl. The substituents could be present, particularly substituents with respect to the group C = X when one or more of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 is a phenyl group.

In the especially preferred embodiments, R4, R5, R6 or R8 are C6_6 alkyl or C6_10 aralkyl, especially methyl, benzyl or PhCHCH3.

In certain highly preferred embodiments, X is a group of the formula (NR3R4) + Q "and R1 and R3 are linked in such a way that when taken together with the carbon atom and the nitrogen atom of the group C = X of the compound of the formula (1) a 5, 6 or 7 membered ring is formed, R4 is C6.10 aralkyl alkyl, especially methyl, benzyl or PhCHCH3 and R2 is optionally substituted hydrocarbyl, preferably C1.6 alkyl or phenyl optionally substituted especially methoxy, hydroxy or fluoro-substituted phenyl The 5-, 6- or 7-membered ring formed by the linking of R1 and R3 could optionally be fused to another ring system, preferably a benzenoid system which could be substituted, preferred substituents include hydroxy, methoxy and fluoro.

More advantageously, the compound of the formula (1) is prochiral, so that the hydrogenated product comprises a chiral atom to which R1, R2 and X are each linked. Such hydrogenation process by asymmetric transfer forms an especially preferred aspect of the present invention. More commonly, when the compound of the formula (1) is prochiral, R1 and R2 are different, and none is hydrogen. Advantageously, one of R1 and R2 is aliphatic and the other is aryl or heterocyclyl.

Examples of the compounds of the formula (1) include wherein R2 and R4 are as defined above and G1 and G3 are independently hydrogen, chloro, bromo, iodo, cyano, nitro, hydroxy, amino, thiol, acyl, hydrocarbyl, perhalogenated hydrocarbyl, heterocyclyl, hydrocarbyloxy, mono- or di- hydrocarbyl, hydrocarbyl, esters, carbonates, amides, sulfonyl and sulfonamido, wherein the hydrocarbyl groups are as defined for R1 above.

Hydrogen donors include hydrogen, primary and secondary alcohols and primary and secondary amines, carboxylic acids and their esters and amine salts, readily dehydrogenatable hydrocarbons, cleaning reducing agents and any combination thereof.

The primary and secondary alcohols that could be used as hydrogen donors commonly comprise from 1 to 10 carbon atoms, preferably from 2 to 7 carbon atoms, and more preferably 3 or 4 carbon atoms. Examples of the primary and secondary alcohols that could be represented as hydrogen donors include methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol, butan-2-ol, cyclopentyl, cyclohexanol, benzyl alcohol and menthol. When the hydrogen donor is an alcohol, secondary alcohols, especially propan-2-ol and butan-2-ol, are preferred.

The primary and secondary amines that could be used as hydrogen donors commonly comprise from 1 to 20 carbon atoms, preferably from 2 to 14 carbon atoms, and more preferably 3 or 8 carbon atoms. Examples of the primary and secondary amines that could be represented as hydrogen donors include ethylamine, propylamine, isopropylamine, butylamine, isobutylamine, hexylamine, diethylamine, dipropylamine, di-isopropylamine, dibutyl amine, di-isobutyl amine, dihexylamine, benzylamine, dibenzylamine and piperidine. . When the hydrogen donor is an amine, primary amines are preferred, especially the primary amines comprising a secondary alkyl group, particularly isopropylamine and isobutylamine.

The carboxylic acids or their esters that could be used as hydrogen donors commonly comprise from 1 to 10 carbon atoms, preferably 1 to 3 carbon atoms. In certain embodiments, the carboxylic acid is advantageously a beta-hydroxy carboxylic acid. The esters could be derived from the carboxylic acid and a C1.10 alcohol. Examples of carboxylic acids that could be used as hydrogen donors include formic acid, lactic acid, ascorbic acid and mandelic acid. The most preferred carboxylic acid is formic acid. In certain preferred embodiments, when a carboxylic acid is used as a hydrogen donor, at least some of the carboxylic acid is preferably present as a salt, preferably an amine, ammonium or metal salt. Preferably, when a metal salt is present, the metal is selected from the alkali or ferrous alkali metals of the periodic table, and is more preferably selected from group I elements, such as lithium, sodium or potassium. The amines that could be used to form such salts include aromatic and non-aromatic amines, also primary, secondary and tertiary amines and typically comprise from 1 to 20 carbon atoms. Tertiary amines, especially trialkylamines, are preferred. Examples of the amines that could be used to form salts include trimethylamine, triethylamine, di-i sopropylethylamine and pyridine. The most preferred amine is triethylamine. When at least one of the carboxylic acids is present as an amine salt, particularly when a mixture of formic acid and triethylamine is employed, the molar ratio of the acid to the amine is between 1: 1 and 50: 1 and preferably between 1: 1 and 10: 1, and more preferably about 5: 2. When at least some of the carboxylic acids are present as a metal salt, particularly when a mixture of formic acid and a metal of group I is used, the molar ratio of the acid to the metal ions present is between 1: 1 and 50: 1. and preferably between 1: 1 and 10: 1, and more preferably about 2: 1. The ratios of the acid to the salts could 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 could be used as hydrogen donors comprise hydrocarbons that are prone to aromatization or hydrocarbons that are prone to form highly conjugated systems. Examples of the readily dehydrogenatable hydrocarbons that could be used as hydrogen donors include cyclohexadiene, cyclohexene, tetralin, dihydrofuran and terpenes.

Reduction reduction reducing agents that could be represented as hydrogen donors comprise reducing agents with a high reduction potential, particularly those that have a reduction potential in relation to the standard hydrogen electrode greater than about -0.1 eV, often higher of about -0.5 eV, and preferably greater than -1 eV. Examples of cleaning reducing agents that could be represented as hydrogen donors include hydrazine and hydroxylamine.

The most preferred hydrogen donors are propan-2-ol, butan-2-ol, triethylammonium formate and a mixture of triethylammonium formate and formic acid. However, in certain embodiments, when the compound of Formula (1) is a protonated iminium salt, it may be desirable to employ a hydrogen donor that is not a carboxylic acid or a salt thereof.

The optionally substituted hydrocarbyl neutral ligand or perhalogenated hydrocarbyl which could be represented by R 15 includes optionally substituted aryl and alkenyl ligands.

The optionally substituted aryl ligands that could be represented by R15 could contain 1 ring or 2 or more fused rings including cycloalkyl, aryl or heterocyclic rings. Preferably, the ligand comprises a 6-membered aromatic ring. The ring or rings of the aryl ligand are frequently substituted with hydrocarbyl groups. The substitution pattern and the number of substituents will vary and could be influenced by the number of rings present, but hydrocarbyl substituent groups, preferably 2, 3 or 6 hydrocarbyl groups and more preferably 6 hydrocarbyl groups are frequently present. Preferred hydrocarbyl substituents include methyl, ethyl, iso-propyl, methyl, neomenthyl and phenyl. Particularly, when the aryl ligand is a single ring, the ligand is preferably benzene or a substituted benzene. When the ligand is a perhalogenated hydrocarbyl, it is preferably a perhalogenated benzene, such as hexachlorobenzene or hexaf luorobenzene. When the hydrocarbyl substituents contain enantiomeric centers and / or tereomeric dias, it is preferred that the enantiomeric and / or diastereomerically purified forms thereof are used. Especially preferred ligands are benzene, p-cymyl, mesitylene and hexamethylbenzene.

The optionally substituted alkenyl ligands that could be represented by R15 include C2_30 alkenes or cycloalkenes and preferably C6_12 with preferably two or more carbon-carbon double bonds, preferably only two carbon-carbon double bonds. The carbon-carbon double bonds could optionally be conjugated to other unsaturated systems that might be present, but are preferably conjugated to one another. The alkenes or cycloalkenes could be preferably substituted with hydrocarbyl substituents. When the alkene has only one double bond, the optionally substituted alkenyl ligand could comprise two separate alkenes. Preferred hydrocarbyl substituents include methyl, ethyl, iso-propyl and phenyl. Examples of the optionally substituted alkenyl ligands include cyclo-octa-1,5-diene and 2,5-norbornadiene. Especially preferred is oct-a-1,5-diene cyclo.

When it is already A or B it is a middle group represented by -NR16-, -NHR16, NR16R17, - NR20-, -NHR20 or NR19R20 where R17 and R19 are as of f ini e ant e ri orment e, and wherein R16 or R20 is an acyl group represented by -C (0) R18 or -C (0) R21, R18 and R21 are often independently C1_1 alkyl, cycloalkyl or linear or branched aryl, phenyl example. Examples of acyl groups that could be represented by R 16 or R 20 include benzoyl, acetyl and halogenoacetyl groups, especially trifluoroacetyl.

When either A or B is present as a sulfonamide group represented by -NR16-, NHR16, NR16R17, -NR20-, -NHR20 or NR19R20 wherein R17 and R19 are as defined above, and wherein R16 or R20 is a group sulfonyl represented by -S (0) 2R18 or -S (0) 2R21, R18 and R21 are independently often C8 alkyl, C1.8 cycloalkyl or linear or branched aryl, for example phenyl. Preferred sulfonyl groups include methanesulfonyl, trifluoromethanesulfonyl and especially p-toluenesulfonyl groups and naphthyl sulphonyl groups.

When either A or B are present as a group represented by -NR16-, NHR16, NR16R17, -NR20-, -NHR20 or NR19R20 where R17 and R19 are as defined above, and wherein R16 or R20 is a group represented by C (0) NR18R22, C (S) NR18R22, C (= NR22) SR23, C (= N R22) OR Z3 C (O) NR ¿¿11RD 24 C (S) N R2Z 11RD 24 C (= N R24 ) SR, 25 o C (= NR24) OR25, R18 and R21 are often independently straight or branched C1_8 alkyl, such as methyl, ethyl, isopropyl, cycloalkyl Cx.a or aryl groups, for example phenyl and R22"are frequently each independently hydrogen or alkyl linear or branched, such as methyl, ethyl, isopropyl, C1_a cycloalkyl or aryl groups, for example phenyl.

When B is present as a group represented by OR19, -SR19, -PR19- or -PR19R21, R19 and R, 21 are independently often linear or branched Cx_8 alkyl, such as methyl, ethyl, isopropyl, cycloalkyl C ^ or aryl, for example phenyl.

It will be recognized that the precise nature of A and B will be determined by whether A and / or B are formally linked to the metal or its coordinate to the metal via a pair of isolated electrons.

The groups A and B are connected by a linking group E. The linking group E achieves a suitable conformation of A and B to allow A and B to bind or coordinate to the metal, M. A and B are commonly linked by means of 2, 3 or 4 atoms. The atoms in E that link A and B could carry one or more substituents. The atoms in E, especially the alpha atoms with respect to A or B, could bind to A and B, such that a heterocyclic ring, preferably a saturated ring, and particularly a 5, 6 or 7 membered ring is formed. Such a ring could be fused to one or more other rings. Frequently, the atoms that link A and B will be carbon atoms. Preferably, one or more of the carbon atoms linking A and B will carry substituents in addition to A or B. The substituent groups include those which could substitute R1., as defined above. Advantageously, any such substituent groups are selected to be groups that do not coordinate with the metal, M. Preferred substituents include halogen, cyano, nitro, sulfonyl, hydrocarbyl, perhalogenated hydrocarbyl and heterocyclyl groups as defined above. The most preferred substituents are C ± _6 alkyl groups and phenyl groups. More preferably, A and B are linked by 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 could comprise part of an aromatic or aliphatic cyclic group, particularly a 5, 6 or 7 membered ring. Such a ring could be fused to one or more of other such rings. Particularly, the embodiments in which E represents a separation of 2 carbon atoms 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 comprising an cyclopentane or cyclohexane ring, optionally fused to a phenyl ring.

It preferably comprises part of a compound having at least one tereospecific center. Wherein any of the 2, 3 or 4 atoms that link A and B are substituted to define at least one tereospecific center on one or more of these atoms. It is preferred that at least one of the centers is tereospecific is located in the atom adjacent to any group A or B. When at least one of the centers is present, it is advantageously present 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 Compounds that could be represented by AEB, or of which AEB could be derived by deprotonation, are frequently aminoalcohols, which include 4-aminoalkan-1-alols, l-aminoalkan-4-alols, 3-aminoxa or 1 can-1- or 1 is, 1-ami noa 1 can-3 - or 1 is, and especially 2-aminoalkan-1-ols, 1-aminoalkan-2-ols, 3-aminoalkan-2-ols and 2-aminoalkan-3-ols , and particularly 2-amino-anoles or 3-aminopropanols, or diamines, which include 1,4-diaminoalkanes, 1,3-diaminoalkanes, especially 1,2- or 2,3-diaminoalkanes and particularly the ethylene diamines. The aminoalcohols that could be represented by A-E-B are 2-aminociclopentanoles and 2-aminociclohexanoles, preferably fused to a phenyl ring. Additional diamines that could be represented by A-E-B are 1,2, -di aminoci open and 1,2-diaocyclohexanes, preferably fused to a phenyl ring. The amino groups could advantageously be N-tosylated. When a diamine is represented by A-E-B, preferably at least one group is N-tosylated. When a diamine is represented by A-E-B, preferably at least one amino is N-tosylated. The aminoalcohols or diamines are advantageously substituted, especially in the linker group, E, by at least one alkyl group, such as a Cx_4 alkyl, and in particular a methyl group or at least one aryl group, particularly a phenyl group.

Specific examples of such compounds that can be represented by A-E-B and the protonated equivalents from which they could be derived are: H2N OH HO - (NH2 HO NH2 Hr) - NHW2 to Preferably, the enantomeric and / or diastereomerically purified forms thereof are used. Examples include (1S, 2R) - (+) - norepinephrine, (1R, 2S) - (+) - cis-1-amino-2-indanol, (1S, 2R) -2-amino-1, 2-diphenylethanol , (1S, 2R) - (-) -cis-l-amino-2-indanol, (IR, 2S) - (-) -noref redin, (S) - (+) - 2 - a mi no - 1 - phenylethanol, (IR, 2 S) -2-amino-1,2-di-phenyl-t-anol, N-tosyl- (IR, 2R) -1, 2-diphenylethylene diamine, N-tosyl- (1S, 2S) -1, 2 -di feni leti lendi amine, (lR, 2S) -cis-l, 2- indandiamine, (ÍS, 2R) -cis-1, 2-indandiamine, (R) - (-) - 2-pyrrolidinemethanol and (S) ) - (+) -2-pyrrolidinemethanol.

Metals that could be represented by M include metals that are capable of catalyzing hydrogenation by transfer. Preferred metals include transition metals, more preferably Group VIII metals of the periodic table, especially ruthenium, rhodium or iridium. When the metal is ruthenium, it is preferably present in the valence state II. When the metal is rhodium or iridium, it is preferably present in the valence state I.

The anionic groups that could be represented by Y include hydride, hydroxy, hydrocarbyloxy, hydrocarbylamino and halogen groups. Preferably, when a halogen is represented by Y, the halogen is chloride. When a hydrocarbyloxy or hydrocarbylamino group is represented by Y, the group could be derived from the deprotonation of the hydrogen donor used in the reaction.

The basic ligands that could be represented by Y include water, Cx_4 alcohols, primary or secondary Cx_8 amines 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, R15 and Y are chosen so that the catalyst is chiral. When such is the case, an enantiomerically and / or diastereomerically purified form is preferably employed. 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-E-B.

The process is carried out preferably in the presence of a base, especially when Y is not a vacant site. The pKa of a base is preferably at least 8.0, especially at least 10.0. Suitable bases are alkali metal hydroxides, alkoxides and carbonates; tertiary amines and quaternary ammonium compounds. The preferred bases are sodium 2-propoxide and triethylamine. When the hydrogen donor is not an acid, the amount of the base used can be up to 5.0, commonly up to 3.0, often up to 2.5 and spatially in the range of 1.0 to 3.5, per moles of the catalyst. When the hydrogen donor is an acid, the catalyst could be contacted with a base before the introduction of the hydrogen donor. In such a case, the molar ratio of the base to the catalyst before the introduction of the hydrogen donor is frequently from 1: 1 to 3: 1, and preferably approximately 1: 1.

Although gaseous hydrogen may be present, the process is normally operated in the absence of gaseous hydrogen, since it seems to be unnecessary.

Advantageously, the process is carried out in the substantial absence of carbon dioxide.

When the dehydrogenation product or products of the hydrogen donor is volatile, for example boiling below 100 ° C, the removal of this volatile product is preferred. The removal can be carried out by distillation, preferably lower than atmospheric pressure or by the use of inert gas dispersion. When using reduced pressure distillation, the pressure frequently is not greater than 500 mmHg, commonly not greater than 200 mmHg, preferably in the range of 5 to 100 mmHg, and more preferably 10 to 80 mmHg. When the product or products of the dehydrogenation of the hydrogen donor is a gaseous material, for example when formic acid is present as a hydrogen donor, the removal is most preferably carried out by the use of inert gas dispersion, for example with nitrogen.

Appropriately, the process is carried out at temperatures in the range of less than 78 to more. of 150'C, preferably from less than 20 to more than 110'C and more preferably, from less than 5 to more than 60 * C. The initial concentration of the substrate, a compound of the formula (1), is appropriately in the range of 0.05 to 1.0 and, for convenient operation at a higher scale, it can be, for example, up to 6.0, more especially 0.25 to 2.0, on a molar basis. The molar ratio of the substrate to the catalyst is suitably not less than 50: 1 and may be up to 50000: 1, preferably between 100: 1 and 5000: 1 and more preferably between 200: 1 and 2000: 1. The hydrogen donor is preferably used in a molar excess on the substrate, especially 5 to 20 times or, if allowed for convenience, greater, for example, up to 500 times. After the reaction, the mixture is made by standard procedures.

During the reaction, a solvent, preferably a polar solvent, more preferably a polar aprotic solvent, for example acetonitrile, dimethylformamide or dichloromethane, could be present. Conveniently, the hydrogen donor could be the solvent when the hydrogen donor is liquid at the reaction temperature, or it could be used in combination with a diluent. Usually, it is preferred to operate in the substantial absence of water, but the water does not appear to inhibit the reaction. If the hydrogen donor or the reaction solvent is not miscible in water and the desired product is soluble in water, it may be desirable to have water present as a second phase that extracts the product, promoting equilibrium and preventing the loss of optical purity of the product as the reaction proceeds. The concentration of the substrate could be chosen to optimize the reaction time, the yield and the enantomeric excess.

The catalytic species are believed to be substantially as depicted in the above formula. It could be used as an oligomer or metathesis product, on a solid support or could be generated in situ.

In certain embodiments, it has been found that certain catalysts are preferred for the hydrogenation by transfer of the iminium salts. The catalysts in which A-E-B is derived from N-tosyldiamines, preferably mono-N-tosyldiamines, mono-N-tosylated ethi-lendiamines are particularly preferred. Especially, M is also ruthenium (II) and R15 represents an aryl group or M is iridium (I) or rhodium (I) and R15 is cyclo-octadiene. In addition, triethylamine is preferably used as a base, a mixture of formic acid and triethylamine in the preferred ratio of 5: 2 (formic acid: triethylamine) is preferably used as a hydrogen donor and the iminium salt is preferably a protonated imine, or it is a methylated or benzylated imine with a iodide counterion, ot or fluoroacetate format. It is believed that when Y is not a vacant site and when M is rhodium or iridium and is in the valence state (I), AEB joins M by means of two dative bonds (the free pairs of the heteroatoms in A and B). they coordinate to M), whereas when M is ruthenium and is in the valence state (II), AEB joins M by means of a dative link or a formal link.

The catalyst can be made by reacting an aryl metal complex or alkenyl halide with a compound of the formula AEB as defined above or a protonated equivalent from which it could be derived, and, where Y represents a vacant site, by reacting the product of the same with a base. The metal aryl or alkenyl halide complex preferably has the formula [MR15Z2] 2 wherein M is ruthenium (II) and has the formula [MR15Z] 2 when M is iridium or rhodium (I), wherein R15 is as defined above and Z represents a halide, particularly chloride.

For the preparation of the catalysts according to the present invention, a solvent is preferably present. The appropriate reaction temperatures are in the range 0-100'C, for example 20-70'C, which often give reaction times of 0.5-24.0 h. After the reaction is completed, the catalyst could be isolated if desired, but conveniently stored as the solution or used as soon after the preparation. The solution may contain the hydrogen donor and this, if it is a secondary alcohol, could be present or used as the solvent for steps (a) and / or (b). The preparation and subsequent handling should preferably be under an inert atmosphere, and particularly under carbon dioxide and oxygen-free conditions.

The catalyst or catalyst solution, in general, is treated with the base either before use in a hydrogenation reaction by transfer or during use. This can be done by adding the base to the catalyst solution, or to the compound of the formula (1) in solution, or by addition to the hydrogenation reaction by transfer.

The iminium salts, in general, can be obtained by methods known in the literature, for example the quaternization of imines, such as by the treatment of imines with alkylating agents.

The transfer hydrogenation can be carried out by transferring the catalyst solution to a solution of the substrate, a compound of the general formula I. Alternatively, a solution of the substrate can be added to a solution of the catalyst. The base could be pre-treated for the solution of the catalyst and / or the substrate solution or can be added later. The hydrogen donor, if not present in the catalyst solution, could be added to the substrate solution or added to the reaction mixture.

The invention is illustrated by the following Examples.

EXAMPLE 1 Reduction of N-methyl-1-phenyl-6,7-dimethoxy-3-dihydroisoquinolinio iodide.

Preparation of catalyst Reagent Weight / vol Weight Mol Molec relation. molar [Ru (p-Cimil) Cl 2] 2 ** 7.6 mg 612 12.4 μmol 1 (R, R) -N-tosyl-1,2- 9.1 mg 366 24.9 μmol 2 diamino-1,2-diphenylethane Preparation of the catalyst Reagent Weight / vol Weight or Mol Molec Relationship, molar Acetonitrile 10 ml Propan- 2 -ol 10 ml No t a s: * * acquired from The Aldri ch Chemi ca l Co Prior to the reaction, all solvents were degassed, for example: 100 ml of anhydrous propan-2-ol was added by syringe to a dry, clean, sealed round bottom flask and degassed; either by reducing the pressure until the solvent started to boil and refilling with nitrogen 3 times, or by bubbling nitrogen through the solution for at least 20 minutes.

The compound (R, R) -N-t-yl-1,2-diamino-1,2-diphenylethane and ruthenium were weighed into a clean, dry Schlenk flask. The flask was covered with a 'Suba seal' (RTM). Their contents were evacuated, then purged at room temperature by 3 changes of nitrogen. The mixture was heated at 80 ° C for 1 hour. The propan-2-ol solvent was then removed and the catalyst was dried at room temperature for 2 hours. The residue was dissolved in acetonitrile to form a 2.49 m solution.

Hydrogenation by transfer Reagent Weight / vol Weight Mol Molec Relationship. molar N-tosyl-1, 2-diamino-l, 2- 2 ml of 4.98 μmol 200 diphenyletan of (R, R) -Ru (p-Soln. Cimil) Cl 2.49 mM N-methyl-1-phenyl-0.409 iodide g 409 1 mmol 6, 7-dimethoxy-3, 4-dihydroisoquinolinio Acetonitrile 2 ml E t3N / HC02H [2: 5] 0.5 ml 6 mmol of 6 of The N-methyl-1-phenyl-6,7-dimethoxy-3,4-dihydroisoquinolinium iodide was dissolved in acetonitrile (2 ml), then degassed. To this was added a solution of the catalyst in acetonitrile (2 ml). The reaction was started by the addition of a triethylamine / formic acid mixture [2: 5]. The reaction was sampled at regular intervals. The samples (0.25 ml) were each made independently by the addition of dichloromethane (4 ml) and washing the organic phase with saturated sodium bicarbonate solution (3 ml). After the organic phase was dried by contacting the solid anhydrous magnesium sulfate and then filtering the solid, the solvent was removed in vacuo. The samples were analyzed by XH NMR.

After 20 hours, the reaction was complete (conversion > 98%).

EXAMPLE 2 Reduction of N-methyl-1-f-enyl-6,7-dimethoxy-3,4-dihydroquinoline iodide.

Preparation of catalyst Reagent Weight / vol Weight Mol Molec relation. molar [Ru (p-Cimil) Cl2] 2 ** 7.6 mg 612 12.4 μmol (R, R) -N-tosyl-1, 2- 9.1 mg 366 24.9 μmol diamino-1,2-diphenylethane Aceonitrile 10 ml Propan- 2-ol 10 ml Notes: ** purchased from The Aldrich Chemical Co Prior to the reaction, all solvents were degassed, for example: 100 ml of anhydrous propan-2-ol was added by syringe to a dry, clean, sealed round bottom flask and degassed; either by reducing the pressure until the solvent started to boil and refilling with nitrogen 3 times, or by bubbling nitrogen through the solution for at least 20 minutes.

The compound (R, R) -N-1os i 1 -1,2-diamino-1,2-diphenylethane and ruthenium were weighed into a clean, dry Schlenk flask. The flask was covered with a 'Suba seal' (RTM). Their contents were evacuated, then purged at room temperature by 3 changes of nitrogen. The mixture was heated at 80 ° C for 1 hour. The propan-2-ol solvent was then removed and the catalyst was dried at room temperature for 2 hours. The residue was dissolved in acetonitrile to form a 2.49 mM solution.

Hydrogenation by transfer Reagent Weight / vol Weight Mol Molec Relationship. molar N-tosyl-1, 2-diamino-l, 2- 3 ml of 7.47 μmol 200 diphenyletan of (R, R) -Ru (p-Soln. Cimil) Cl 2.49 mM N-methyl-1-phenyl-0.614 iodide g 409 1.5 mmol 6, 7-dimethoxy-3, 4-dihydroisoquinolinio Acetonitrile 3 ml E t 3N / HC02H [2: 5] 0.75 ml 9 mmo l of 6 HC02H HC02H The N-met il-l-phenyl-6,7-dimethoxy-3,4-dihydroisoquinolinio iodide was dissolved in acetonitrile (3 ml), then it degassed. To this was added a solution of the catalyst in acetonitrile (3 ml). The reaction was started by the addition of a triet-ilamine / formic acid mixture [2: 5]. The reaction was sampled at regular intervals. The samples (0.25 ml) were each made independently by the addition of dichloromethane (4 ml) and washing the organic phase with saturated sodium bicarbonate solution (3 ml). After drying the organic phase by contacting the solid anhydrous magnesium sulfate and then filtering the solid, the solvent was removed in vacuo. The samples were analyzed by 1 H NMR.

After 2 days, the reaction was complete (conversion > 99%) with 69% ee.

EXAMPLE 3 to 6 General Procedures Prior to the reaction, all solvents were degassed, for example: 100 ml of anhydrous acetonitrile was added by syringe to a dry, clean, sealed round bottom flask and degassed; either by reducing the pressure until the solvent started to boil and refilling with nitrogen 3 times, or by bubbling nitrogen through the solution for at least 20 minutes.

The t-riet-ilamine / formic acid mixture used as the reducing system was prepared as follows. Freshly distilled formic acid (41.5 ml, 50.6 g, 1.1 mol) was added slowly to triethylamine (58.8 ml, 44.82 g, 0.44 mol) with stirring and cooled with ice (ice bath) under a nitrogen atmosphere to provide a mixture which consisted of a 5: 2 molar ratio of formic acid: triethylamine.

Preparation of the initiating materials.

Preparation of N-methy1-1-phenyl-6,7-dimethoxy-3,4-dihydroisoquinolinio iodide Reagent Weight or Weight mMol Relationship vol Molec. molar Methyl iodide * 0.94 ml 142 15 1.5 Acetone * 50 ml 409 1.5 mmol l-phenyl-6,7-dimethoxy-3, 4- 2.67 g 267 dihydroisoquinoline * * * Purchased from The Aldrich Chemical Co ** Acquired from ACROS To a stirred solution of l-phenyl-6,7-dimethoxy-3,4-dihydroisoquinol ina in acetone was added methyl iodide and the reaction mixture was stirred at room temperature for 16 hours. A pale yellow precipitate formed. The by-products and the unreacted methyl iodide were removed in vacuo to provide the desired compound in 93% yield.

Preparation of N-methyl-1-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinio iodide Reagent Weight or Weight mMol Relationship vol Molec. molar Methyl iodide * 0.6 ml 142 10 Acetone * 250 ml l-methyl-6,7-dimethoxy-3, 4-1025 g 205 dihydroisoquinoline ** * Purchased from The Aldrich Chemical Co ** Acquired from ACROS To a stirred solution of l-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline in acetone was added methyl iodide and the reaction mixture was stirred at room temperature for 16 hours. A light yellow precipitate formed. The by-products and unreacted methyl iodide were removed in vacuo to provide the desired compound in 95% yield.

Preparation of N-benzyl-l-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinio bromide Reagent Weight or Weight mMol Relationship vol Molec. molar Benzyl bromide * 1.71 g 171 10 Acetone * 10 ml l-methyl-6,7-dimethoxy-3, 4- 1.00 g 205 4.8 di idroi soquinol ina ** * Purchased from The Aldrich Chemical Co. .. ** Acquired from ACROS To a stirred solution of 1-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline in acetone was added benzyl bromide and the reaction mixture was stirred at room temperature for 16 hours. A yellow precipitate formed, which was filtered, washed with ice-cold acetone and dried in vacuo. The product was then purified by recrystallization from a mixture of hexane / dichloromethane and pentane to provide the desired compound in 81% yield Preparation of N-benzyl indolonium bromide Reagent Weight or Weight mMol Relationship vol Molec. molar Benzyl bromide * 10.52 g 171 62 Acetone * 70 ml Indolnin 5.00 g 159 31 ^ Purchased from The Aldrich Chemical Co To a stirred solution of indolnine in acetone was added benzyl bromide and the reaction mixture was stirred at room temperature for 16 hours. A precipitate formed which was filtered and dried in vacuo. The product was then purified by recrystallization from a mixture of hexane / dichloromethane and pentane to provide the desired compound in 10% yield.

Transformation Hydrogenation Reactions EXAMPLE 3 Hydrogenation by Transfer of iodide of N-methyl 'l-phenyl-6,7-dimethoxy-3, -dihydroisoquinolinio Reagent Weight or Weight mMol Relationship vol Molec. molar [Ru (p- cimi l) Cl2] 2 * 2.3 mg 612 0.00375 0.5 (R, R) -N-tosyl-1, 2- 2.8 mg 366 0.0075 diamino-1,2-diphenylethane Triethylamine / Acid 0.75 ml 9 (wrt of 1200 (formic wrt (molar ratio of acid 2/5) formic) formic) Acetonitrile 5 ml N-methyl-1-methyl-0.610 g iodide 407 1.5 200 6, 7 -dime oxy-3, -dihydroisoquinolinio ^ Compound purchased from The Aldrich Chemical Company ** Compound purchased from The Fisher Scientific.

The (R, R) -N-1-yl-1,2-di-amino-1, 2-diphenylene dimer, ruthenium dichloride and N-methyl-l-phenyl-6,7-dimethoxy-3 iodide, 4-dihydroisoquinolinio were weighed in a dry, clean Schlenk flask. The flask was capped with a 'Suba seal' (RTM), evacuated, then refilled with nitrogen 3 times. The solids were dissolved in acetonitrile and a nitrogen dispersion was applied. The reaction mixture was stirred for 5-10 minutes before the formic acid / triethylamine mixture was added to start the reaction. The reaction was sampled at regular intervals. The samples (0.25 ml) were made immediately by the addition of dichloromethane (4 ml) and the organic phase was washed with saturated sodium bicarbonate solution (4 ml). After drying the organic phase with solid anhydrous magnesium sulfate and after filtering the solid, the solvent was stirred in vacuo to give a white powder. The samples were analyzed by chiral HPLC. After 2 hours, the reaction was 87% complete and after 7 hours the reaction was > 98% complete, forming the desired product in -60% ee.

EXAMPLE 4 Hydrogenation by transfer of iodide of N-methyl-l-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinio Reagent Weight or Weight mMol Relationship vol olec. molar [Ru (p-cimil) Cl2] 2- '1.6 mg 612 0.0025 0.5 (R, R) -N-tosyl-1, 2- 1.8 mg 366 0.005 diamino-1,2-di-f-enylethane iso-Propanol j 19 ml excess sodium iso-propoxide, in 1.5 ml 0.1M 0.15 i-PrOH N-methyl-1-methyl-0.347 g iodide 347 200 6,7-dimethoxy-3,4-dihydroisoquinolinio ^ Compound purchased from The Aldrich Chemical Company ** Compound purchased from The Fisher Scientific.

The (R, R) -N-1-yl-1,2-diamino-1,2-diphenylethane dimer and ruthenium dichloride were weighed into a clean, dry Schlenk flask. The flask was covered with a 'Suba stamp' (RTM), it was evacuated, then it was refilled with nitrogen 3 times. The solids were dissolved in iso-propanol. The reaction mixture was stirred overnight, before it was added with iodide of N-meth i 1-1-met i 1-6,7-dimethoxy-3,4-dihydroisoquinolinio. Once the solids had dissolved, the sodium isopropoxide was added in an aliquot to begin the reaction. The reaction mixture was heated to 40 * C and stirred.

The reaction was sampled at regular intervals. The samples (0.25 ml) were prepared immediately. The solvent was removed in vacuo and the residue was placed in dichloromethane (4 ml). The organic phase was washed with saturated sodium bicarbonate solution (4 ml). After drying the organic phase with solid anhydrous magnesium sulfate and after filtering the solid, the solvent was removed to give an almost white powder. The samples were analyzed by H NMR and the ee was determined by chiral HPLC.

After 48 hours, the reaction was 72% complete forming the desired product with 63% ee.

EXAMPLE 5 Hydrogenation by transfer of N-benzyl-l-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinio bromide Reagent Weight or Weight mMol Relationship vol Molec. molar [Ru (p-cimil) Cl2] 2 * 1.6 m < J 612 0.0025 0.5 (R, R) -N-tosyl-1, 2- mg 366 0.005 diamino-1,2-diphenylethane Iso-Propanol ** 19 ml excess sodium iso-propoxide, in 1.5 ml 0.1M 0.15 i-PrOH N-benzyl-1- 0.376 g bromide 376 200 methyl-6,7-dimethoxy-3,4-dihydroisoquinolinio ^ Compound purchased from The Aldrich Chemical Company ** Compound purchased from The Fisher Scientific.

Dimer (R, R) -N-tosyl-1,2-diamino-1,2-diphenylethane and ruthenium dichloride were weighed in a dry Schlenk flask, cleansed. The flask was capped with a 'Suba seal' (RTM), evacuated, then refilled with nitrogen 3 times. The solids were dissolved in iso-propanol. The reaction mixture was stirred overnight, before N-benzyl-1-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinium bromide was added. Once the solids had dissolved, the sodium iso-propoxide was added in an aliquot to begin the reaction. The reaction mixture was heated to 40 ° C and stirred.The reaction was sampled at regular intervals. The samples (0.25 ml) were prepared immediately. The solvent was removed and the residue was placed in dichloromethane (4 ml). The organic phase was washed with saturated sodium bicarbonate solution (4 ml). After drying the organic phase with solid anhydrous magnesium sulfate and after filtering the solid, the solvent was stirred in vacuo to provide an almost white powder. The samples were analyzed by 1 H NMR and the ee was determined by chiral HPLC.

After 48 hours, the reaction was 73% complete to form the desired product with 69% ee.

EXAMPLE 6 Hydrogenation by transfer of N-benzyl-indolonium bromide Reagent Weight or Weight mMol Relationship vol Molec. molar [Ru (p-cimil) Cl2] 2 * 1.53 mg 612 0.0025 0.5 (R, R) -N-tosyl-1, 2- 1.8 mg 366 0.005 1 diamino-1,2-dif enylethane Tri ethylamine / acid 1 ml 29 (wrt 5800 (formic wrt (molar ratio of acid of acid 1/50) formic) formic) Acetonitrile ** 3 ml N-benzyl bromide - 1.34 g 159 200 indolonium * Compound purchased from The Aldrich Chemical Company. ** Compound purchased from The Fisher Scientific.

Dimer (R, R) -N-tosyl-1,2-diamino-1,2-diphenylethane, ruthenium dichloride and N-benzyl indolinium bromide were weighed in a clean, dry Schlenk flask. The flask was capped with a 'Suba seal' (RTM), evacuated, then refilled with nitrogen 3 times. The solids were dissolved in acetonitrile. The reaction mixture was stirred for 5-10 minutes, before bromide was added to the formic acid / triethylamine mixture to start the reaction.

The reaction was sampled at regular intervals. The samples (0.25 ml) were made immediately by the addition of dichloromethane (4 ml) and the organic phase was washed with saturated sodium bicarbonate solution (4 ml). After drying the organic phase with solid anhydrous magnesium sulfate and after filtering the solid, the solvent was stirred in vacuo to give a white powder. The samples were analyzed by 1ti NMR.

After 22 hours, the reduction was > 98% complete.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (14)

CLAIMS Having described the invention as above, property is claimed as contained in the following. 1. A process for the hydrogenation by transfer of a compound of the formula (1) X R ^ R2 (D characterized because X represents (NR3R4) + Q_, N + R5-0_, (NR60R7) + Q_,: NR8NR9R O) + Q-, (NR8NR9C (= NR) R12) + Q ", (NR8NR9S02R13) +", OR NR8NR9COR14) + Q "; Q ~ represents a monovalent anion; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 each independently represents a hydrogen atom, an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group, one or more of R1 & R2, R1 & R3, R2 & R \ R3 & R4, R1 & R5, R1 & R6, R2 & R7, R1 & R8, R1 & R9, R6 & R7, R8 & R9 and R9 & R10 which are optionally linked in such a manner to form an optionally substituted ring or rings; Y R 12 R 13 and R 14 each independently represent an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group; the process comprises reacting the compound of the formula (1) with a hydrogen donor in the presence of a catalyst, characterized in that the catalyst has the general formula: ,AND. \, B M 15 Y R where : R15 represents an optionally substituted hydrocarbyl or perhalogenated hydrocarbyl ligand;
1. A represents -NR16-, -NRi 17. -NHR16, -NR, 1166RD 17 O-NR17R18 wherein R16 is H, C (0) R18, S02R18, C (0) NR18R22, C (S) NR18R22, C (= NR22) SR23 or C (= NR22) OR23, R17 and R18 each independently represents an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group and R22 and R23 are each independently hydrogen or a group as defined for R18; B represents -O-, OH, OR19, -S-, -SH, SR19, -NR19-, -NR20-, NHR20-, -NR19R20, -NR19R21, -PR19- or -PR19R21 wherein R20 is H, C ( 0) R21, S02R21, C (0) NR21R24, C (S) NR21R24, C (= NR24) SR25 or C (= NR24) OR25, R19 and R21 each independently represent a substituted hydrocarbyl, perhalogenated hydrocarbyl or a heterocyclyl group optionally substituted, and R24 and R25 are each, one independently hydrogen or a group as defined for R21; E represents a linking group; M represents a metal capable of catalyzing hydrogenation by transfer; and Y represents an anionic group, a basic ligand or a vacant site; with the proviso that when Y is not a vacant site that is at least one of A or B that carries a hydrogen atom.
2. 2. A process according to claim 1, characterized in that X represents (NR3R4) + Q and, R1, R2, R3 and R4 each independently represents an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group, or one or more of R1 & R2, R1 & R3, R2 & R4 and R3 & R4 which are optionally linked in such a manner to form an optionally substituted ring (s).
3. 3. A process according to either of. claims 1 or 2, characterized in that M is a transition metal of group VIII, especially ruthenium, rhodium or iridium.
4. 4. A process according to any of claims 1 to 3, characterized in that R15 is an optionally substituted aryl or an optionally substituted alkene.
5. 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 optionally substituted ethylenediamine. .
6. 6. A process according to claim 5, characterized in that either A or B carry an acyl or sulfonyl group, preferably a toluenesulfonyl, methanesulfonyl, tri fluorometanesulfonyl or acetyl group.
7. 7. A process according to claim 5, characterized in that A-E-B is, or is derived from, one of the following: H, N > -T OH HO r < NH, HO NH2 H ^ NH2
8. 8. A process according to any of the preceding claims, characterized in that the compound of the formula (1) is prochiral and the catalyst is chiral, an enantomeric and / or diastereomerically purified form of the catalyst that is employed, whereby the compound of Formula (1) is hydrogenated asymmetrically.
9. 9. A process according to claim 8, characterized in that A-E-B comprises at least one stereospecific center.
10. 10. A process 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, reducing agents of cleaning and any combination thereof.
11. 11. A process according to claim 10, characterized in that the hydrogen donor is a mixture of triethylamine and formic acid.
12. 12. A process according to any of claims 1 to 11, characterized in that the products of the dehydrogenation of the hydrogen donor are removed by inert gas dispersion or vacuum distillation.
13. 13. A process according to any of claims 1 to 12, characterized in that a compound of the formula (1) is hydrogenated by transfer in the presence of a catalyst wherein A-E-B is, or is derived from, an N-1-osityl amine.
14. 14. 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. PROCESS OF HYDROGENATION BY TRANSFER SUMMARY OF THE INVENTION A hydrogenation process is provided by catalytic transfer. The catalyst used in the process is a metal-neutral hydrocarbyl complex that coordinates to defined bidentate ligands. Preferred metals include rhodium, ruthenium and iridium. Preferred bidentate ligands are diamines and aminoalcohols, particularly those comprising chiral centers. The hydrogen donor is advantageously a mixture of triethylamine and formic acid. The process can be used to transfer the hydrogenated iminium salts, which are preferably prochiral.