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WO2001004131A1 - Diphosphine ligands for metal complexes - Google Patents

Diphosphine ligands for metal complexes Download PDF

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Publication number
WO2001004131A1
WO2001004131A1 PCT/EP2000/006658 EP0006658W WO0104131A1 WO 2001004131 A1 WO2001004131 A1 WO 2001004131A1 EP 0006658 W EP0006658 W EP 0006658W WO 0104131 A1 WO0104131 A1 WO 0104131A1
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Prior art keywords
alkyl
substituted
phenyl
unsubstituted
alkoxy
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PCT/EP2000/006658
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French (fr)
Inventor
Benoît PUGIN
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Solvias Ag
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Priority to AU59846/00A priority Critical patent/AU5984600A/en
Priority to EP00945913A priority patent/EP1194437A1/en
Priority to JP2001509740A priority patent/JP2003504376A/en
Publication of WO2001004131A1 publication Critical patent/WO2001004131A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/5027—Polyphosphines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B35/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving a change in the type of bonding between two carbon atoms already directly linked
    • C07B35/02—Reduction
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/0073—Rhodium compounds
    • C07F15/008—Rhodium compounds without a metal-carbon linkage
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F17/00—Metallocenes
    • C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings

Definitions

  • the invention relates to ditertiary diphosphine ligands for metal complexes as hydrogenation catalysts which are soluble in a polar reaction medium, for example water and organic solvents such as methanol, due to solubilizing groups and which can easily be separated from the reaction mixture after the hydrogenation, possibly by changing the pH.
  • a polar reaction medium for example water and organic solvents such as methanol
  • Hydrogenation processes which may be enantioselective or diastereoselective, using metal complexes of, for example, rhodium, iridium or ruthenium and achiral or chiral ditertiary diphosphine ligands have become important processes for the synthesis of intermediates or active substances such as pesticides and pharmaceuticals.
  • aqueous or polar reaction media are often the medium of choice because of the solubility of starting compounds, but this then also requires water-soluble hydrogenation catalysts which can easily be separated from the reaction product by extraction.
  • EP-A-0 329 043 describes pyrrolidine diphosphines bound to polyethylene glycol via a diisocyanate bridge; the rhodium complexes of these are used for the hydrogenation of 2,3-dehydrophosphinothricin - ⁇ - derivatives in aqueous solution.
  • the stoichiometric composition of the complexes is difficult to control, so that reproducibility is not always ensured.
  • Pyrrolidine diphosphines bound to a polyacrylic acid suffer from the same problem: although their complexes are water-soluble, the loading with the diphosphine is not sufficiently controllable [T. Malmstr ⁇ m et al., J. of Mol. Cat. A: Chemical 139, pages 259-270 (1999)].
  • the enantioselectivity depends on the loading with the diphosphine and the catalyst activity is relatively low.
  • ligands for hydrogenation catalysts which are soluble in a polar reaction medium, have a good catalyst activity, enable high optical yields to be achieved when the hydrogenation catalysts are chiral, can be used in the acidic to basic range of an aqueous reaction medium to set optimized reaction conditions, can be used in polar solvents such as alcohols, have a high catalyst activity even at high ratios of substrate to catalyst, for example above 100, lead to high optical yields and can easily be separated from the reaction mixture.
  • the invention provides, firstly, compounds of the formulae I and la, A-[[Si-(C 1 -C 4 alkyl) 2 ] x -C m H 2m -Xi-C(0)-X 1 '- C n H 2n -Y ! -(R-Y) y ] r (I),
  • A is a monovalent to tetravalent framework of a ditertiary diphosphine bound via a C atom
  • Ai is a monovalent framework of a 3-8-membered N- heterocyclic ditertiary diphosphine bound via the N atom
  • Xi is -0-, -NH- or -N- (C ⁇ -Calkyl) -,
  • Xi' is -NH- or -N- (C ⁇ -C 4 alkyl)-; or X 1 ' is -O- when Xi is -NH- or -N-(C ⁇ -C 4 alkyl)-,
  • Y is -C0 2 M, -N(C ⁇ -C 4 alkyl) 2 -, -N(C ⁇ -C alkyl) 2 H + X 2 " or -N(C ⁇ -C 4 alkyl) 3 + X 2 " ,
  • x is 1 and m is from 2 to 4, or x is 0, m is 0 or an integer from 1 to 4, n is 0 or an integer from 1 to 4, r is an integer from 1 to 4, y is an integer from 1 to 5,
  • M is H, an alkali metal or a monovalent hydrocarbon radical having from 1 to 18 C atoms, and
  • X 2 is the anion of an inorganic or organic acid.
  • the ditertiary diphosphines can be ones in which the phosphine groups are bound (a) to various C atoms of a chain having from 2 to 6 C atoms, preferably a carbon chain having from 2 to 4 C atoms, or (b) directly or via a bridging group of the formula -CR a Rb- either in the ortho positions of a cyclopentadienyl ring or each to a cyclopentadienyl ring of a ferrocenyl group, where R a and R b are identical or different and are H, Ci- C 8 alkyl, C ⁇ -C 4 fluoroalkyl, C 5 -C 6 cycloalkyl, phenyl, benzyl, or phenyl or benzyl substituted by from 1 to 3 C ⁇ -Calkyl or C ⁇ -C 4 alkoxy groups.
  • R b is preferably hydrogen.
  • R a is preferably hydrogen or C ⁇ -C 4 alkyl.
  • the individual phosphine groups may contain identical or different hydrocarbon radicals.
  • the individual phosphine groups preferably contain two identical hydrocarbon radicals, with various phosphine groups of this type being able to be bound to the framework of the diphosphine.
  • the hydrocarbon radicals can be unsubstituted or substituted and contain from 1 to 20, preferably from 1 to 12, C atoms.
  • the individual phosphine groups contain two identical or different radicals selected from the group consisting of linear or branched C ⁇ -C ⁇ alkyl; unsubstituted or C ⁇ -C 6 alkyl- or C ⁇ -C 6 alkoxy- substituted C 5 -C ⁇ 2 cycloalkyl or C 5 -C ⁇ 2 cycloalkyl-CH 2 -; phenyl and benzyl; and phenyl or benzyl substituted by halogen (for example F , CI and Br ) , C ⁇ -C 6 alkyl , Ci-Cehaloalkyl ( for example trif luoromethyl ) , Ci- C 6 alkoxy , C ⁇ -C 6 haloalkoxy ( for example trifluoro- methoxy ) , ( C 6 H 5 ) 3 Si , ( d-C ⁇ 2 alkyl ) 3 Si or
  • the two radicals in the phosphine groups can also together be unsubstituted or halogen- , C ⁇ -C 6 alkyl- or C ⁇ -C 6 alkoxy-substituted dimethylene , trimethylene , tetramethylene , pentamethylene or 3 -oxapentane-l , 5- diyl .
  • the substituents are preferably bound in the two ortho positions relative to the P atom .
  • the phosphine groups can also be groups of the formulae
  • o and p are, independently of one another, an integer from 2 to 10, and the sum of o+p is from 4 to 12 and preferably from 5 to 8.
  • Examples are [3.3.1]- and [4.2.1] -phobyl of the formulae
  • alkyl substituents preferably containing from 1 to 6 C atoms
  • alkyl substituents preferably containing from 1 to 6 C atoms
  • P alkyl substituents, preferably containing from 1 to 6 C atoms, on P are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl and the isomers of pentyl and hexyl.
  • Examples of unsubstituted or alkyl- substituted cycloalkyl substituents on P are cyclopentyl, cyclohexyl, methylcyclohexyl and ethylcyclohexyl and dimethylcyclohexyl.
  • alkyl-, alkoxy-, haloalkyl- and haloalkoxy-substituted phenyl and benzyl substituents on P are methylphenyl, dimethylphenyl, trimethylphenyl, ethylphenyl, methylbenzyl, methoxyphenyl, dimethoxyphenyl, trifluoro ethylphenyl, bistrifluoromethylphenyl, tristrifluoromethylphenyl, trifluoromethoxyphenyl and bistrifluoromethoxyphenyl .
  • Preferred phosphine groups are those containing identical or different, preferably identical, radicals selected from the group consisting of C ⁇ -C 6 alkyl, unsubstituted or C ⁇ -C 4 alkyl- or C ⁇ -C 4 alkoxy- monosubstituted to -trisubstituted cyclobutyl, cyclopentyl or cyclohexyl, benzyl and particularly phenyl which is unsubstituted or substituted by from 1 to 3 C ⁇ -C 4 alkyl, C ⁇ -Calkoxy, F, CI, C ⁇ -C 4 fluoroalkyl or C ⁇ -C 4 fluoroalkoxy substituents.
  • diphosphine radicals A and Ai in the formulae I and la preferably correspond to the formulae II, Ila and lib,
  • Ri , R 2 , R 4 and R 5 are each, independently of one another, a hydrocarbon radical having from 1 to 20 C atoms which is unsubstituted or substituted by halogen, C ⁇ -C 6 alkyl , Ci-Cehaloalkyl , C ⁇ -C 6 alkoxy, C ⁇ -C 6 haloalkoxy, ( C 6 H 5 ) 3 Si , (C ⁇ -C ⁇ 2 alkyl) 3 Si or -C0 2 -Ci-C 6 alkyl ; or R x and R 2 or R 4 and R 5 are in each case together unsubstituted or halogen- , C ⁇ -C 6 alkyl- or C ⁇ -C 6 alkoxy-substituted tetramethylene, pen tame thy lene or 3 -oxapentane-l , 5-diyl ; and R 3 is unsubstituted or C ⁇ -C 6 alkyl- , C
  • R 8 is hydrogen, C ⁇ -C 8 alkyl, C ⁇ -C 4 fluoroalkyl, unsubstituted phenyl or phenyl substituted by from 1 to 3 F, CI, Br, C ⁇ -Calkyl, C ⁇ -C 4 alkoxy or fluoromethyl substituents;
  • q in formula Ila is 0 or an integer from 1 to 6, where the radical of the formula Ila is unfused or fused with cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic radicals, and the radical of the formula Ila is unsubstituted or substituted by halogen, C ⁇ -C 6 alkyl, C ⁇ -C 6 haloalkyl, C ⁇ -C 6 alkoxy, C ⁇ -C 6 haloalkoxy, (C 6 H 5 ) 3 Si, (C ⁇ -C ⁇ 2 alkyl) 3 Si or -C0 2 -Ci-C 6 alkyl; and R 9 and Rio are, independently of one another, C
  • R 9 and Rio are preferably methylene, ethylene or linear or branched propylene or butylene .
  • the chain formed by R 9 , Rio and N preferably contains from 3 to 5 atoms.
  • Ri, R 2 , R and R 5 are preferably identical or different, in particular identical, radicals selected from the group consisting of branched C 3 -C 6 alkyl, unsubstituted or C ⁇ -C 4 alkyl- or C ⁇ -C 4 alkoxy-monosubstituted to -trisubstituted cyclopentyl or cyclohexyl, unsubstituted or C ⁇ -C 4 alkyl- or C ⁇ -C 4 alkoxy- monosubstituted to -trisubstituted benzyl and in particular unsubstituted or C ⁇ -C 4 alkyl-, C ⁇ -C 4 alkoxy-, NH 2 -, OH-, F-, C1-, C ⁇ -C 4 fluoroalkyl- or C ⁇ -C 4 fluoro- alkoxy-monosubstituted to -trisubstituted phenyl.
  • R is preferably C ⁇ -C 8 alkyl and particularly preferably C ⁇ -C 6 alkyl which may be interrupted by from one to three -0- or -N(C ⁇ -C 4 alkyl) - groups .
  • the alkyl in the group N(C ⁇ -C 4 alkyl) 2 is preferably linear and can be methyl, ethyl, n-propyl or n-butyl .
  • Y is particularly preferably -C0 2 M, -N(CH 3 ) 2 -, -N(CH 3 ) 2 H + X 2 " or -N(CH 3 ) 3 + X 2 ⁇ in which M is H, Li, Na, K or C ⁇ -C 4 alkyl, and X 2 is the anion of an inorganic or organic acid.
  • M is H, Li, Na, K or C ⁇ -C 4 alkyl
  • X 2 is the anion of an inorganic or organic acid.
  • m is preferably 0, 1 or 2 and n is preferably 0, 1 or 2.
  • r is preferably from 1 to 3, particularly preferably 1 or 2 and very particularly preferably 1.
  • y is preferably from 1 to 4, particularly preferably from 1 to 3 and very particularly preferably 1 or 2.
  • a cycloalkane radical Y 2 is preferably a 5- or 6-membered cycloalkane radical.
  • the alkyl is preferably methyl .
  • alkali metals M preference is given to Li, Na or K.
  • Anions X 2 derived from an inorganic acid may be, for example, halides such as chloride, bromide and iodide, sulfite, sulfate, hydrogensulfate, carbonate, hydrogen- carbonate, nitrate, phosphite, hydrogenphosphite, phosphate, hydrogenphosphate, tetrafluoroborate or hexafluorophosphate.
  • halides such as chloride, bromide and iodide, sulfite, sulfate, hydrogensulfate, carbonate, hydrogen- carbonate, nitrate, phosphite, hydrogenphosphite, phosphate, hydrogenphosphate, tetrafluoroborate or hexafluorophosphate.
  • Anions X 2 derived from organic acids are the anions of carboxylic acids, sulfonic acids and phosphonic acids which may contain from 1 to 18, preferably from 1 to 12 and particularly preferably from 1 to 8, C atoms.
  • Some preferred examples of anions of organic acids are acetate, propionate, butyrate, monochloroacetate, dichloroacetate and trichloroacetate, monofluoro- acetate, difluoroacetate and trifluoroacetate, hydroxyacetate, oxalate, malonate, and also the anions of cyclohexanemonocarboxylic and cyclohexane- dicarboxylic acids, benzoic acid, phthalic and terephthalic acids, trifluoromethylbenzoic acid, phenylacetic acid, phenylphosphonic acid, methyl- sulfonic, ethylsulfonic, propylsulfonic, butylsulfonic, cyclo
  • the group - [Si- (C ⁇ -C 4 alkyl) 2 ] x -C m H 2m -X ⁇ - in the radicals of the formula I is preferably -Si (CH 3 ) 2 -CH 2 CH 2 CH 2 -NH- or -Si(CH 3 ) 2 -CH 2 CH 2 CH 2 -0-.
  • Some specific embodiments of the group -CmH ⁇ - are methylene, ethylene, 1,2- or 1, 3-propylene, 1,2-, 1,3-, 1,4- or 2,3-butylene, ethylidene, propylidene and butylidene.
  • Some specific embodiments of the group -X ⁇ -C(O) -X x ' - C n H 2n -Y ⁇ - (R-Y)y in the radicals of the formula I are, for example, -NH-C(O) -NH-C (CH 2 -C0 2 H) 3 , -NH-C (O) -NH-CH(CH 2 - C0 2 H) 2 , -NH-C(0)-NH-CH 2 (CH 2 -C0 2 H) , -NH-C (O) -NH-CH 2 -C (CH 2 - C0 2 H) 3 , -NH-C(0)-NH-CH 2 -CH(CH 2 -C0 2 H) 2 -NH-C (0) -NH-CH 2 - CH 2 (CH 2 -C0 2 H) , -0-C(0)-NH-C(CH 2 -C0 2 H) 3 , -O-C (O) -NH-CH(CH 2 -
  • NHC 6 H 8 (N(CH 3 ) 2 ) 3 , -0-C(0)-NHC 6 H 9 (N(CH 3 ) 2 ) 2/ -O-C (O) -NHC 6 H 8 - (N(CH 3 ) 2 ) 3 .
  • a (CH 3 ) 2 N group can be replaced by a (C 2 H 5 ) 2 N group.
  • Particularly preferred groups are -NH-C (O) -NH-C (CH 2 -0- CH 2 CH 2 C0 2 H) 3 , -O-C (O) -NH-C (CH 2 -0-CH 2 CH 2 C0 2 H) 3 , -NH-C(O)- NH-CH 2 CH 2 -N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 , -NH-C (O) -NH-CH 2 -NH-CH 2 CH 2 - N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 and -NH-C (O) -N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 , where the N(CH 3 ) 2 group can be replaced by an N(C 2 H 5 ) 2 group.
  • Some specific embodiments of the group -C (0) -Xi' -C n H 2n - Yi-(R-Y) y are ones as listed above but in which -NH- or -0- is left off at the beginning.
  • Particularly preferred groups are -C(O) -NH-C (CH 2 -0-CH 2 CH 2 C0 2 H) 3 , -C (0) -NH-CH 2 C (CH 2 -0-CH 2 CH 2 C0 2 H) 3 , -C (O) -NH-CH 2 CH 2 -N[CH 2 CH 2 - N(CH 3 ) 2 ] 2 and -C (O) -NH-CH 2 CH 2 CH 2 -N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 , where the N(CH 3 ) 2 group can be replaced by an N(C 2 H 5 ) 2 group.
  • a preferred subgroup of tertiary diphosphines of the formulae I and la consists of those of the formulae
  • Rii and R i2 are, independently of one another, linear or branched C ⁇ -C 4 alkylene, and the chain -P-Rn-N-R ⁇ 2 -P- has from 5 to 8 atoms,
  • R13 and R i are identical or different groups selected from among unsubstituted or C ⁇ -Calkyl-, C ⁇ -C 4 alkoxy- or trifluoromethyl-substituted C 5 cycloalkyl or C 6 cycloalkyl and unsubstituted or C ⁇ -C 4 alkyl-, C ⁇ -Calkoxy-, F-, Cl- or trifluoromethyl-substituted phenyl,
  • R15 and R ⁇ 6 are together C 2 -C 6 alkylene
  • R i are, independently of one another, a bond or methylene or ethylidene
  • L is a radical of the formula -C(O) -Xi' -C n H 2n -Y ! - (R-Y) y and
  • Li is a radical of the formula - [ [Si- (CH 3 ) 2 ] x -C m H 2m -X ⁇ -
  • Xi' is -NH- or -N- (C ⁇ -C 4 alkyl) -; or Xi ' is -0- when X x is
  • Y is -C0 2 M, -N(CH 3 ) 2 , -N(CH 3 ) 2 H + X 2 " or -N(CH 3 ) 3 + X 2 " , x is 1 and m is 2 or 3 , or x is 0, m is 0 or from 2 to 4, n is 0 or from 2 to 4, r is 1 or 2, y is an integer from 1 to 3 , M is H, Li, Na, K or Ci-C 4 alkyl, and
  • X 2 is the anion of an inorganic or organic acid.
  • X 2 can be, for example, an anion selected from the group consisting of chloride, bromide, iodide, hydrogensulfate, dihydrogenphosphate, acetate, benzoate, tosylate and methylsulfonate.
  • the compounds of the formulae I and la can be prepared in a manner known per se by reacting OH- or NH- functional ditertiary disphosphines with isocyanates or capped isocyanates of a solubilized compound.
  • the invention further provides a process for preparing compounds of the formulae I and la, in which a) OH- or NH-functional ditertiary diphosphines of the formulae III and Ilia,
  • esters for example methyl or ethyl esters
  • carboxylic acids Y is -C0 2 H
  • Activated urea derivatives are also referred to as capped isocyanates. These can, for example, correspond to the formula IVa,
  • Y, Y x , R, n, y and r are as defined above and R19 is the N-bonded radical of an activating amine.
  • Such amines are essentially cyclic secondary amines, preferably N-heteroaromatics such as pyrrole and in particular imidazole.
  • the compounds of the formulae IV and IVa are obtainable by reaction of appropriate ureas, for example carbonylbisimidazole, with compounds of the formula H 2 N-C n H 2n -Y ⁇ - (R-Y) y ] r •
  • mixtures of isocyanates and capped isocyanates in chemical equilibrium can be formed and can likewise be used.
  • the reaction is generally carried out at room temperature or slightly elevated temperature in an inert solvent such as toluene.
  • the reaction products can be used directly in further reactions without isolating the isocyanates/capped isocyanates. Syntheses using azolidene are described by H. A. Staab in Angew. Chem. 12, 1962, pages 407 to 419.
  • the reaction of functional ditertiary diphosphine and isocyanate/capped isocyanate or vice versa is generally carried out in an inert solvent.
  • suitable solvents are aliphatic, cycloaliphatic or aromatic hydrocarbons, halogenated hydrocarbons, ethers, carboxylic esters, lactones, N-substituted carboxamides, lactams and ketones.
  • the reaction can be carried out at temperatures of from -20 °C to 100 °C.
  • the compounds of the formulae I and la are very useful ligands for metal complexes, in particular ones which can be used as hydrogenation catalysts and are soluble in polar reaction media such as water or aprotic or protic and polar organic solvents, e.g. alcohols, and can be separated off after the hydrogenation, for example by means of extraction, if appropriate after hydrolysis of ester groups and/or changing the pH.
  • polar reaction media such as water or aprotic or protic and polar organic solvents, e.g. alcohols
  • the invention further provides metal complexes of d 8 metals with compounds of the formulae I and la, in particular metal complexes of the formulae V, Va and Vb
  • a 3 is a compound of the formula I or la;
  • X is two monoolefin ligands or one diene ligand;
  • Me is a d 8 metal selected from the group consisting of Ir and Rh;
  • D is -CI, -Br or -I;
  • E is the anion of an oxo acid or complex acid;
  • X 3 and X 4 are identical or different and are as defined for D or E, or X 3 and X 4 are allyl or 2-methallyl, or X 3 is as defined for D or E and X 4 is hydride.
  • D is -Cl, -Br or -I.
  • E " is C10 " , CF 3 S0 3 " , CH 3 S0 3 “ , HS0 4 “ , BF 4 " , B (phenyl) 4 “ , PF 6 “ , SbCl 6 “ , AsF 6 “ or SbF 6 " .
  • the metal complexes of the formulae V, Va and Vb are prepared by methods known from the literature.
  • the metal complexes of the invention are very useful as catalysts for the hydrogenation of organic double and triple bonds .
  • the metal complexes of the invention are useful for the enantioselective hydrogenation of compounds containing prochiral carbon-carbon and carbon-heteroatom double bonds. Examples of such compounds are prochiral alkenes, imines and ketones.
  • a further aspect of the invention is therefore the use of the novel metal complexes of d 8 metals as heterogeneous or homogeneous catalysts for hydrogenation, preferably for the asymmetric hydrogenation of prochiral compounds having carbon- carbon or carbon-heteroatom double bonds in a polar reaction medium.
  • the metal complexes are preferably used for the asymmetric hydrogenation of prochiral compounds having carbon-carbon or carbon-heteroatom double bonds, in particular the Ir complexes for the hydrogenation of prochiral ketimines and the Rh complexes for the hydrogenation of prochiral ketimines and prochiral alkenes .
  • the invention further provides a process for the hydrogenation of compounds having carbon-carbon or carbon-heteroatom double bonds, which comprises reacting the compounds at a temperature of from -20 to 150 °C with hydrogen in the presence of catalytic amounts of one or more metal complexes of the invention in a polar reaction medium.
  • the metal complexes of the invention are hydrogenation catalysts or precursors of such catalysts which are activated under the hydrogenation conditions.
  • the metal complexes can be prepared in situ and used as hydrogenation catalysts.
  • the hydrogenations are advantageously carried out under protective gas such as noble gases (argon) .
  • the process can be carried out under a hydrogen pressure of from 1 to 500 bar, preferably 1-150 bar, particularly preferably from 1 to 120 bar and in particular from 1 to 100 bar.
  • the reaction temperature can be, for example, from 0 to 150 °C, preferably from 10 to 120 °C and particularly preferably from 30 to 100 °C.
  • the amount of catalyst depends mainly on the desired reaction time and on economic considerations. Higher amounts of catalyst essentially promote shorter reaction times. Catalysts are preferably used in amounts of from 0.0001 to 10 mol%, particularly preferably from 0.001 to 10 mol% and in particular from 0.01 to 5 mol%, based on the compound to be hydrogenated.
  • the molar ratio of substrate to catalyst can be, for example, from 30 to 100000, preferably from 50 to 50000, particularly preferably from 50 to 30000 and in particular from 100 to 2000.
  • a particularly advantageous aspect is that the hydrogenation can be carried out in polar reaction media, for example polar organic or aqueous media, and in the acid, neutral or basic range, so that reaction conditions optimized for a particular substrate can be set and the catalysts can easily be separated off, for example by means of extraction. If Y in the formulae I and la is an ester group, this can be hydrolyzed beforehand to form the acid group.
  • polar reaction media for example polar organic or aqueous media
  • acid, neutral or basic range so that reaction conditions optimized for a particular substrate can be set and the catalysts can easily be separated off, for example by means of extraction. If Y in the formulae I and la is an ester group, this can be hydrolyzed beforehand to form the acid group.
  • an aqueous reaction medium is one consisting of only water or water in admixture with a water-miscible or water-immiscible organic solvent.
  • the proportion of water is preferably at least 30 per cent by volume, particularly preferably at least 50 per cent by volume and in particular at least 70 per cent by volume.
  • the reaction medium very particularly preferably contains only water.
  • suitable solvents are alcohols such as methanol, ethanol, propanol, butanol, ethylene glycol and ethylene glycol monomethyl ether; ethers such as diethyl ether, diisobutyl ether, tetrahydrofuran and dioxane; esters and lactones such as ethyl acetate, methyl acetate and valerolactone; sulfoxides and sulfones such as dimethyl sulfoxide, dimethyl sulfone, tetramethylene sulfone; ketones such as acetone or methyl isobutyl ketone; halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloroethane and chlorobenzene; and N-substituted carboxamides and lactarns such as N-methylpyrrolidone and dimethylformamide. If the organic solvents are not miscible with water, a two-phase hydrogen
  • Buffers, bases or acids can be added to the aqueous reaction medium.
  • the reaction can, for example, be carried out at a pH of from 1 to 12, preferably from 2 to 10 and particularly preferably from 3 to 9.
  • Suitable buffers are, in particular, phosphate buffers, but it is also possible to use carboxylic acids, carbonic acid, phosphoric acid and boric acid.
  • suitable bases are alkali metal hydroxides and alkaline earth metal hydroxides, amines and alkali metal salts of carboxylic acids, carbonic acid, phosphoric acid and boric acid.
  • Suitable acids are HC1, HBr, HI, HBF 4 , HC10 4 , carboxylic acids (unsubstituted, fluorinated or chlorinated acetic acid, benzoic acid, citric acid) , boric acid, phosphoric acid, methanesulfonic acid, sulfuric acid and carbonic acid.
  • the bases and acids can also be soluble or insoluble polymers such as ion-exchange resins .
  • the amount of bases, acids and/or buffers can be, for example, from 0 to 2, preferably from 0 to 1 and particularly preferably from 0 to 0.5, mol per litre of water.
  • suitable organic solvents are esters and lactones such as ethyl acetate and methyl acetate and valerolactone; ketones such as acetone or methyl isobutyl ketone; halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloroethane and chlorobenzene; ethers such as diethyl ether, diisobutyl ether, tetrahydrofuran and dioxane; sulfoxides and sulfones such as dimethyl sulfoxide, dimethyl sulfone, tetramethylene sulfone; N-substituted carboxamides and lactams such as N-methylpyrrolidone and dimethyl- formamide; and particularly alcohols.
  • esters and lactones such as ethyl acetate and methyl acetate and valerolactone
  • ketones such as acetone or methyl isobutyl ket
  • an alcoholic reaction medium means the presence of an alcohol, either alone or in admixture with another organic solvent.
  • Suitable alcohols are aliphatic, cyclo- aliphatic, cycloaliphatic-aliphatic and araliphatic alcohols.
  • Some preferred examples are methanol, ethanol, n- or i-propanol, n-, i- or t-butanol, pentanol, hexanol, cyclohexanol, cyclohexanediol, hydroxymethylcyclohexane or dihydroxymethylcyclohexane, benzyl alcohol, ethylene glycol, diethylene glycol, propanediol, butanediol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, and diethylene glycol monomethyl ether or diethylene glycol monoethyl ether.
  • the proportion of an alcohol is preferably at least 30 per cent by volume, particularly preferably at least 50 per cent by volume and in particular at least 70 per cent by volume. Very particular preference is given to using only an alcohol.
  • the catalytic properties of the diphosphine catalysts used can be influenced by addition of cocatalysts, modifiers, metal halides and ammonium halides. It can therefore be advantageous to add alkali metal or ammonium chlorides, bromides or iodides, for example LiCl, LiBr, Lil, Nal, NaBr or tetrabutylammonium iodide, to the reaction mixture. The amount can be, for example, from 0.001 to 5 mol per litre of solvent.
  • Known modifiers are phthalimides and parabanic acid.
  • the hydrogenation can be carried out continuously or batchwise in various types of reactor. Preference is given to reactors which allow comparatively good mixing and good heat removal, e.g. loop reactors. This type of reactor has been found to be particularly useful when using small amounts of catalyst.
  • the hydrogenated organic compounds which can be prepared according to the invention are active substances or intermediates for preparing such substances, in particular in the production of pharmaceuticals and agrochemicals .
  • o, o-dialkylarylamine derivatives in particular those having alkyl and/or alkoxyalkyl groups, act as fungicides, particularly as herbicides.
  • the derivatives can be amine salts, acid amides, e.g. of chloroacetic acid, tertiary amines and ammonium salts (cf., for example, EP-A-0 077 755 and EP-A-0 115 470) .
  • Example Al Preparation of (C 2 H 5 0 2 C-CH 2 CH 2 -0-CH 2 - ) 3 C-NCO (Al) A solution of 1 mmol of (C 2 H 5 0 2 C-CH 2 CH 2 -0-CH 2 -) 3 C-NH 2 (prepared as described by G.R. Newcome et al . , Aldrichimica Acta, 25 (1992) 31-8)] in toluene (7 ml per mmol) is added to an equimolar amount of carbonyldiimidazole and the mixture is stirred overnight. A mixture of isocyanate and imidazolylurea is formed. The solution is used directly for the reactions below.
  • Example A2 Preparation of H 2 N-CH 2 CH 2 CH 2 -N[CH 2 CH 2 -N- (C 2 H 5 )] 2 (A2) a) A mixture of 1 ml (3.5 mmol) of N,N,N',N'- tetraethyldiethylenetriamine in 5 ml of acetonitrile and 938 mg (3.5 mmol) of N- (3-bromopropyl)phthalimide and 977 mg (7 mmol) of potassium carbonate is stirred at room temperature over the weekend.
  • the reaction mixture is extracted with methylene chloride/water, the organic phase is dried over sodium sulfate and evaporated on a rotary evaporator and the crude product is purified by chromatography (silica gel Merck 60, eluant: 50 / 1 mixture of ethanol / triethylamine) .
  • the product is obtained as an oil in a yield of 80%.
  • Example Bla The procedure of Example Bla is repeated, except that 3 , 4-diphenylphosphinopyrrolidine (pyrphos) is used as starting compound.
  • the reaction product is obtained in a yield of 63%.
  • Example B3 Preparation of ligand K3 a) Preparation of the triester The procedure of Example Bla is repeated, except that
  • Example Bib The procedure of Example Bib is repeated. The product is obtained as a white solid in a yield of 92%.
  • a solution of 83 mg (0.133 mmol) of the amine ligand B in 1.5 ml of methylene chloride is added at 0 °C to a solution of 22 mg (0.133 mmol) of 1, 1 ' -carbodiimidazole in 2 ml of methylene chloride and the mixture is subsequently stirred at room temperature for 2 hours .
  • 2 equivalents of N,N,N' ,N' -tetraethyldiethylenetriamine and 2 mg of dibutyltin dilaurate are then added and the mixture is stirred overnight .
  • Example B7 Preparation of ligand K7 97 mg (0.335 mmol) of tetraamine A2 in 1.5 ml of methylene chloride are added at 0 °C to a solution of 58 mg (0.35 mmol) of 1, 1 '-carbodiimidazole in 4 ml of methylene chloride and the reaction mixture is subsequently stirred at room temperature for 1 hour. A solution of 154 mg (0.34 mmol) of (2S, 4S) - (- ) -4- diphenylphosphino-2- (diphenylphosphinomethyl) - pyrrolidine in 2 ml of methylene chloride is then added and the mixture is stirred under reflux for 6 hours.
  • R H or K, Na: acetamidocinnamic acid (AC)
  • All operations are carried out under argon as protective gas .
  • the hydrogenations are carried out in a 25 ml glass flask (1 bar of hydrogen pressure) or a 50 ml steel autoclave (>1 bar of hydrogen pressure) provided with magnetic stirrer and a vacuum/gas connection.
  • the hydrogenation solutions are introduced by means of a syringe and needle, in the case of the glass flask through a septum, in the case of the autoclave under a countercurrent of argon.
  • the inert gas is displaced by hydrogen (glass apparatus: 4 cycles of vacuum, hydrogen at atmospheric pressure; steel autoclave: 4 cycles of pressurization with 5-10 bar of hydrogen and depressurization) .
  • the hydrogenations are started by switching on the stirrer.
  • pH 7 0.041 mol of Na 2 HP0 4 and 0.028 mol of KH 2 P0 4 /litre
  • pH 8 0.063 mol of Na 2 HP0 4 and 0.004 mol of KH 2 P0 4 /litre .
  • the ligand is placed in a vessel and dissolved while stirring with the aid of 0. IN NaOH (1 equivalent of NaOH per equivalent of carboxylic acid functions) . After addition of 1 ml of water, the ligand solution is added to [Rh(norbornadiene) 2 ]BF 4 and the mixture is stirred until a clear solution is obtained.
  • the substrate solution is prepared as described in Method a, but is made up to 10 ml with water only after addition of the catalyst solution. This solution is transferred to a hydrogenation apparatus and hydrogenated.
  • Method c Hydrogenation in water
  • the ligand is placed in a vessel, suspended in 1 ml of water and dissolved by addition of methanesulfonic acid (1% by volume in water) (1 equivalent of methanesulfonic acid per equivalent of amine functions) .
  • the ligand solution is added to [Rh (norbornadiene) 2 ]BF 4 and the mixture is stirred until a clear solution is obtained.
  • the substrate solution is prepared as described in Method a) , but is made up to 10 ml with water only after addition of the catalyst solution. This solution is transferred to a hydrogenation apparatus and hydrogenated.
  • the hydrogenation solution from Example C9 is, after the hydrogenation, evaporated to dryness under reduced pressure and the mixture is subsequently extracted with ethyl acetate and water (with phosphate buffer, pH 8) .
  • the organic phases are collected, washed with water, dried over sodium sulfate and finally evaporated to dryness on a rotary evaporator. Analysis of the organic product indicates that more than 95% of the rhodium have been separated off.
  • the reaction conditions are indicated in Table 1.
  • MAC is used as substrate, while AC is used in all the others .
  • the hydrogenation in Examples CI and CIO is carried out by Method a) , in Examples C2 to C7 by Method b) , and in Examples C7, C8, Cll, C12 and C15 by Method c) .
  • the hydrogen pressure is 15 bar, in all the other examples 1 bar.
  • the solvent is water; in Examples C8, C9, Cll, C12 and C15 it is methanol; and in Example C5 it is a mixture of 10 ml of water (phosphate buffer pH 8) and 7 ml of ethyl acetate (two-phase hydrogenation) .
  • Reaction temperature in Examples C1-C5 and C10-C11: 25 °C; in Examples C6 to C9 and C12-C15: 40 °C.
  • Examples C16-C23 Hydrogenation of folic acid 0.0025 mmol of ligand are dissolved in 5 ml of water and 0.5 ml of buffer pH 7 (0.041 mol of Na 2 HP0 4 and 0.028 mol of KH 2 P0 4 in 1 1 of water) . The carboxylic acid groups of the ligands are then reacted with 0.1N NaOH until a clear solution is formed. The resulting solution is added to 7.4 mg (0.02 mmol) of [Rh(NBD) 2 ]BF and stirred until a solution has formed (NBD is norbornadiene) .
  • This solution is added to a solution of 2 mmol of folic acid disodium salt in 11 ml of water and 1.5 ml of buffer pH 7 and the mixture is transferred to a hydrogenation autoclave provided with a sparging stirrer by means of a syringe in a countercurrent of argon.
  • the autoclave is closed, the argon is replaced by hydrogen and hydrogen is finally injected until the desired pressure has been reached.
  • the hydrogen pressure is maintained by further supplies from the reservoir via a reducing valve.
  • the hydrogenation is started by switching on the stirrer.
  • the hydrogenation time reported is the time until the reaction stops (no longer any uptake of hydrogen) . Unless indicated otherwise, this corresponds to complete conversion of the folic acid.
  • the pressure is 80 bar and the reaction temperature is 70 °C (30 °C in Example C21) .
  • the molar ratio of substrate to catalyst (S/C) is 100 in Examples C16-C22 and is 1000 in Example C23.
  • the optical yield DE is reported for the S,S configuration of folic acid. The results are summarized in Table 3.
  • Footnotes 1) Buffer pH 6 : 0.01 mol of Na 2 HP0 and 0.071 mol of KH 2 P0 4 in 1 1 of water; at the end of the reaction, another 4 ml of IN KH 2 P0 4 are added.

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Abstract

Chiral or nonchiral ditertiary diphosphines having solubilizing substituents, for example -NH-C(O)-NH-C(CH2-O-CH2CH2CO2H)3, in the diphosphine framework are excellent ligands for d8 metal complexes which are soluble in polar media, for example water or alcohols, and which can be used as asymmetric or symmetric hydrogenation catalysts for compounds having carbon-carbon or carbon-heteroatom double bonds.

Description

Diphosphine ligands for metal complexes
The invention relates to ditertiary diphosphine ligands for metal complexes as hydrogenation catalysts which are soluble in a polar reaction medium, for example water and organic solvents such as methanol, due to solubilizing groups and which can easily be separated from the reaction mixture after the hydrogenation, possibly by changing the pH.
Hydrogenation processes, which may be enantioselective or diastereoselective, using metal complexes of, for example, rhodium, iridium or ruthenium and achiral or chiral ditertiary diphosphine ligands have become important processes for the synthesis of intermediates or active substances such as pesticides and pharmaceuticals. In addition to reactions in organic solvents, aqueous or polar reaction media are often the medium of choice because of the solubility of starting compounds, but this then also requires water-soluble hydrogenation catalysts which can easily be separated from the reaction product by extraction.
Some hydrogenation catalysts soluble in aqueous media are already known. Thus, K. Wan et al . in J. Chem. Soc, Chem. Com., pages 1262-1264 (1993) and I. Toth et al.; Tetrahydron: Asymmetry, Volume 1, pages 913-930 (1990) describe ditertiary diphosphine ligands for such catalysts. In these ligands, the phenyl radicals in the phosphine groups are substituted by either amino or -S03H. However, these substituents change the catalytic properties so that the desired result can often no longer be achieved.
EP-A-0 329 043 describes pyrrolidine diphosphines bound to polyethylene glycol via a diisocyanate bridge; the rhodium complexes of these are used for the hydrogenation of 2,3-dehydrophosphinothricin - Δ - derivatives in aqueous solution. The stoichiometric composition of the complexes is difficult to control, so that reproducibility is not always ensured. Pyrrolidine diphosphines bound to a polyacrylic acid suffer from the same problem: although their complexes are water-soluble, the loading with the diphosphine is not sufficiently controllable [T. Malmstrόm et al., J. of Mol. Cat. A: Chemical 139, pages 259-270 (1999)]. In addition, the enantioselectivity depends on the loading with the diphosphine and the catalyst activity is relatively low.
The use of rhodium complexes of trimellitic acid diphosphinopyrrolidinamide as hydrogenation catalysts in aqueous medium (0.1 mol of Na2HP04) has also already been proposed. However, the catalyst activity and the optical yields achieved in the hydrogenation of acetamidocinnamic acid are too low.
There is a need for ligands for hydrogenation catalysts which are soluble in a polar reaction medium, have a good catalyst activity, enable high optical yields to be achieved when the hydrogenation catalysts are chiral, can be used in the acidic to basic range of an aqueous reaction medium to set optimized reaction conditions, can be used in polar solvents such as alcohols, have a high catalyst activity even at high ratios of substrate to catalyst, for example above 100, lead to high optical yields and can easily be separated from the reaction mixture.
It has now surprisingly been found that these objects are achieved when a group which has a solubilizing effect in polar reaction media and may be hydrolyzable is bound to the framework of a ditertiary diphosphine via a urethane or carbamate group.
The invention provides, firstly, compounds of the formulae I and la, A-[[Si-(C1-C4alkyl)2]x-CmH2m-Xi-C(0)-X1'- CnH2n-Y!-(R-Y)y]r (I),
A1-C(0)-Xι'-CnH2n-Y1-(R-Y)y (la),
in which
A is a monovalent to tetravalent framework of a ditertiary diphosphine bound via a C atom, Ai is a monovalent framework of a 3-8-membered N- heterocyclic ditertiary diphosphine bound via the N atom,
Xi is -0-, -NH- or -N- (Cι-Calkyl) -,
Xi' is -NH- or -N- (Cι-C4alkyl)-; or X1' is -O- when Xi is -NH- or -N-(Cι-C4alkyl)-,
is a direct bond, -0-, -N=, -CH=,
\
(y+l)-valent benzene radical, or a (y+l)-valent radical of a 3-8-membered cycloalkane, where n is from 1 to 4 when Yi is -O- or -N=, R is a linear or branched, (y+l)-valent radical of a
Cι-C12alkane which may be uninterrupted or interrupted by -0-, -N= or -N(Cι-C4alkyl)-, or
R is a direct bond and Yi is not -0- or -N=,
Y is -C02M, -N(Cι-C4alkyl)2-, -N(Cι-C alkyl) 2H+X2 " or -N(Cι-C4alkyl)3 +X2 ", x is 1 and m is from 2 to 4, or x is 0, m is 0 or an integer from 1 to 4, n is 0 or an integer from 1 to 4, r is an integer from 1 to 4, y is an integer from 1 to 5,
M is H, an alkali metal or a monovalent hydrocarbon radical having from 1 to 18 C atoms, and
X2 is the anion of an inorganic or organic acid.
A large number of achiral and chiral ditertiary diphosphines for hydrogenation catalysts are described in the literature, cf., for example, H. Brunner and W. Zettlmeier, Handbook of Enantioselective Catalysis, Vol. II: Ligand References, VCH Verlagsgesellschaft mbH Weinheim (1993). Ditertiary diphosphines functionalized with hydroxyl or amine groups are likewise known or can be prepared by known or analogous methods. If the hydrogenation catalysts contain chiral ditertiary diphosphines as ligands, asymmetric inductions for enantioselective or diastereoselective hydrogenations can frequently be achieved. According to the invention, the radicals A and Ai can be either chiral or achiral ditertiary diphosphines .
The ditertiary diphosphines can be ones in which the phosphine groups are bound (a) to various C atoms of a chain having from 2 to 6 C atoms, preferably a carbon chain having from 2 to 4 C atoms, or (b) directly or via a bridging group of the formula -CRaRb- either in the ortho positions of a cyclopentadienyl ring or each to a cyclopentadienyl ring of a ferrocenyl group, where Ra and Rb are identical or different and are H, Ci- C8alkyl, Cχ-C4fluoroalkyl, C5-C6cycloalkyl, phenyl, benzyl, or phenyl or benzyl substituted by from 1 to 3 Cι-Calkyl or Cι-C4alkoxy groups. Rb is preferably hydrogen. Ra is preferably hydrogen or Cι-C4alkyl. The individual phosphine groups may contain identical or different hydrocarbon radicals. The individual phosphine groups preferably contain two identical hydrocarbon radicals, with various phosphine groups of this type being able to be bound to the framework of the diphosphine. The hydrocarbon radicals can be unsubstituted or substituted and contain from 1 to 20, preferably from 1 to 12, C atoms. Among the ditertiary diphosphines, particular preference is given to ones in which the individual phosphine groups contain two identical or different radicals selected from the group consisting of linear or branched Cι-Cιalkyl; unsubstituted or Cι-C6alkyl- or Cι-C6alkoxy- substituted C5-Cι2cycloalkyl or C5-Cι2cycloalkyl-CH2-; phenyl and benzyl; and phenyl or benzyl substituted by halogen ( for example F , CI and Br ) , Cι-C6alkyl , Ci-Cehaloalkyl ( for example trif luoromethyl ) , Ci- C6alkoxy , Cι-C6haloalkoxy ( for example trifluoro- methoxy ) , ( C6H5 ) 3Si , ( d-Cι2alkyl ) 3Si or -C02-Ci-C6alkyl ( for example -C02CH3 ) .
The two radicals in the phosphine groups can also together be unsubstituted or halogen- , Cι -C6alkyl- or Cι-C6alkoxy-substituted dimethylene , trimethylene , tetramethylene , pentamethylene or 3 -oxapentane-l , 5- diyl . The substituents are preferably bound in the two ortho positions relative to the P atom .
The phosphine groups can also be groups of the formulae
Figure imgf000006_0001
in which o and p are, independently of one another, an integer from 2 to 10, and the sum of o+p is from 4 to 12 and preferably from 5 to 8. Examples are [3.3.1]- and [4.2.1] -phobyl of the formulae
Figure imgf000006_0002
Examples of alkyl substituents, preferably containing from 1 to 6 C atoms, on P are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl and the isomers of pentyl and hexyl. Examples of unsubstituted or alkyl- substituted cycloalkyl substituents on P are cyclopentyl, cyclohexyl, methylcyclohexyl and ethylcyclohexyl and dimethylcyclohexyl. Examples of alkyl-, alkoxy-, haloalkyl- and haloalkoxy-substituted phenyl and benzyl substituents on P are methylphenyl, dimethylphenyl, trimethylphenyl, ethylphenyl, methylbenzyl, methoxyphenyl, dimethoxyphenyl, trifluoro ethylphenyl, bistrifluoromethylphenyl, tristrifluoromethylphenyl, trifluoromethoxyphenyl and bistrifluoromethoxyphenyl .
Preferred phosphine groups are those containing identical or different, preferably identical, radicals selected from the group consisting of Cι-C6alkyl, unsubstituted or Cι-C4alkyl- or Cι-C4alkoxy- monosubstituted to -trisubstituted cyclobutyl, cyclopentyl or cyclohexyl, benzyl and particularly phenyl which is unsubstituted or substituted by from 1 to 3 Cι-C4alkyl, Cι-Calkoxy, F, CI, Cι-C4fluoroalkyl or Cι-C4fluoroalkoxy substituents.
The diphosphine radicals A and Ai in the formulae I and la preferably correspond to the formulae II, Ila and lib,
(II),
R,R,P — R,— PR4R5
lRIP
Figure imgf000007_0001
Figure imgf000007_0002
in which
Ri , R2 , R4 and R5 are each, independently of one another, a hydrocarbon radical having from 1 to 20 C atoms which is unsubstituted or substituted by halogen, Cι-C6alkyl , Ci-Cehaloalkyl , Cι-C6alkoxy, Cι-C6haloalkoxy, ( C6H5 ) 3Si , (Cι-Cι2alkyl) 3Si or -C02-Ci-C6alkyl ; or Rx and R2 or R4 and R5 are in each case together unsubstituted or halogen- , Cι-C6alkyl- or Cι-C6alkoxy-substituted tetramethylene, pen tame thy lene or 3 -oxapentane-l , 5-diyl ; and R3 is unsubstituted or Cι-C6alkyl- , Cι-C6alkoxy- , C5cycloalkyl- or C6cycloalkyl- , phenyl- , naphthyl- or - - benzyl-substituted C2-C4alkylene; unsubstituted or Cι-C6alkyl-, phenyl- or benzyl-substituted 1,2- or 1,3- cycloalkylene, 1,2- or 1, 3-cycloalkenylene, 1,2- or 1, 3-bicycloalkylene or 1,2- or 1, 3-bicycloalkenylene having from 4 to 10 C atoms; unsubstituted or Cι-C6alkyl-, phenyl- or benzyl-substituted 1,2- or 1,3- cycloalkylene, 1,2- or 1, 3-cycloalkenylene, 1,2- or 1, 3-bicycloalkylene or 1,2- or 1, 3-bicycloalkenylene having from 4 to 10 C atoms to which methylene or C2-C4alkylidene is bound in the 1 and/or 2 positions or in the 3 position; 1,4-butylene which is substituted by R6RC(0-)2 in the 2,3 positions and is unsubstituted or substituted by Cι-C6alkyl, phenyl or benzyl in the 1 and/or 4 positions, where R6 and R7 are, independently of one another, hydrogen, Cι-C6alkyl, phenyl or benzyl; 3,4- or 2, 4-pyrrolidinylene or methylene-4-pyrrolidin- 4-yl whose N atom is substituted by hydrogen, Cι-Cι2alkyl, phenyl, benzyl, Cι-Cι2alkoxycarbonyl, Cι-C8acyl, Cι-Cι2alkylaminocarbonyl; or unsubstituted or halogen-, -OH-, Cι-C6alkyl-, Cι-C6alkoxy- , phenyl-, benzyl-, phenyloxy- or benzyloxy-substituted 1,2- phenylene, 2-benzylene, 1, 2-xylylene, 1, 8-naphthylene, 2,2' -binaphthylene or 2,2' -biphenylene ; or R3 is a radical of the formulae
Figure imgf000008_0001
Figure imgf000008_0002
C CHHERLι- ,
Figure imgf000008_0003
in which R8 is hydrogen, Cι-C8alkyl, Cι-C4fluoroalkyl, unsubstituted phenyl or phenyl substituted by from 1 to 3 F, CI, Br, Cι-Calkyl, Cι-C4alkoxy or fluoromethyl substituents; q in formula Ila is 0 or an integer from 1 to 6, where the radical of the formula Ila is unfused or fused with cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic radicals, and the radical of the formula Ila is unsubstituted or substituted by halogen, Cι-C6alkyl, Cι-C6haloalkyl, Cι-C6alkoxy, Cι-C6haloalkoxy, (C6H5)3Si, (Cι-Cι2alkyl)3Si or -C02-Ci-C6alkyl; and R9 and Rio are, independently of one another, Cι-C4alkylene.
R9 and Rio are preferably methylene, ethylene or linear or branched propylene or butylene . The chain formed by R9, Rio and N preferably contains from 3 to 5 atoms.
Ri, R2, R and R5 are preferably identical or different, in particular identical, radicals selected from the group consisting of branched C3-C6alkyl, unsubstituted or Cι-C4alkyl- or Cι-C4alkoxy-monosubstituted to -trisubstituted cyclopentyl or cyclohexyl, unsubstituted or Cι-C4alkyl- or Cι-C4alkoxy- monosubstituted to -trisubstituted benzyl and in particular unsubstituted or Cι-C4alkyl-, Cι-C4alkoxy-, NH2-, OH-, F-, C1-, Cι-C4fluoroalkyl- or Cι-C4fluoro- alkoxy-monosubstituted to -trisubstituted phenyl.
In the formulae II and Ila, Yi is preferably -N=, -CH= or a quaternary C atom.
In the formulae II and Ila, R is preferably Cι-C8alkyl and particularly preferably Cι-C6alkyl which may be interrupted by from one to three -0- or -N(Cι-C4alkyl) - groups .
The alkyl in the group N(Cι-C4alkyl)2 is preferably linear and can be methyl, ethyl, n-propyl or n-butyl .
In the formulae II and Ila, Y is particularly preferably -C02M, -N(CH3)2-, -N(CH3 ) 2H+X2 " or -N(CH3) 3 +X2\ in which M is H, Li, Na, K or Cι-C4alkyl, and X2 is the anion of an inorganic or organic acid. In the formulae II and Ila, m is preferably 0, 1 or 2 and n is preferably 0, 1 or 2.
In the formulae II and Ila, r is preferably from 1 to 3, particularly preferably 1 or 2 and very particularly preferably 1.
In the formulae II and Ila, y is preferably from 1 to 4, particularly preferably from 1 to 3 and very particularly preferably 1 or 2.
In the formulae II and Ila, a cycloalkane radical Y2 is preferably a 5- or 6-membered cycloalkane radical.
In the group Si (Cι-C4alkyl) 2, the alkyl is preferably methyl .
As alkali metals M, preference is given to Li, Na or K.
Anions X2 derived from an inorganic acid may be, for example, halides such as chloride, bromide and iodide, sulfite, sulfate, hydrogensulfate, carbonate, hydrogen- carbonate, nitrate, phosphite, hydrogenphosphite, phosphate, hydrogenphosphate, tetrafluoroborate or hexafluorophosphate.
Anions X2 derived from organic acids are the anions of carboxylic acids, sulfonic acids and phosphonic acids which may contain from 1 to 18, preferably from 1 to 12 and particularly preferably from 1 to 8, C atoms. Some preferred examples of anions of organic acids are acetate, propionate, butyrate, monochloroacetate, dichloroacetate and trichloroacetate, monofluoro- acetate, difluoroacetate and trifluoroacetate, hydroxyacetate, oxalate, malonate, and also the anions of cyclohexanemonocarboxylic and cyclohexane- dicarboxylic acids, benzoic acid, phthalic and terephthalic acids, trifluoromethylbenzoic acid, phenylacetic acid, phenylphosphonic acid, methyl- sulfonic, ethylsulfonic, propylsulfonic, butylsulfonic, cyclohexylsulfonic, phenylsulfonic, methylphenyl- sulfonic, trifluoromethylphenylsulfonic, monochlorome- thylsulfonic, dichloromethylsulfonic and trichloro- methylsulfonic and monofluoromethylsulfonic, difluoromethylsulfonic and trifluoromethylsulfonic acids. Particular preference is given to the anions of unsubstituted and substituted phenylsulfonic acids.
The group - [Si- (Cι-C4alkyl) 2]x-CmH2m-Xι- in the radicals of the formula I is preferably -Si (CH3) 2-CH2CH2CH2-NH- or -Si(CH3)2-CH2CH2CH2-0-.
Some specific embodiments of the group -CmH^- are methylene, ethylene, 1,2- or 1, 3-propylene, 1,2-, 1,3-, 1,4- or 2,3-butylene, ethylidene, propylidene and butylidene.
Some specific embodiments of the group -Xι-C(O) -Xx ' - CnH2n-Yι- (R-Y)y in the radicals of the formula I are, for example, -NH-C(O) -NH-C (CH2-C02H)3, -NH-C (O) -NH-CH(CH2- C02H)2, -NH-C(0)-NH-CH2(CH2-C02H) , -NH-C (O) -NH-CH2-C (CH2- C02H)3, -NH-C(0)-NH-CH2-CH(CH2-C02H)2 -NH-C (0) -NH-CH2- CH2(CH2-C02H) , -0-C(0)-NH-C(CH2-C02H)3, -O-C (O) -NH-CH(CH2- C02H)2, -0-C(0)-NH-CH2(CH2-C02H) , -O-C (O) -NH-CH2-C (CH2- C02H)3, -0-C(0)-NH-CH2-CH(CH2-C02H)2, -O-C (O) -NH-CH2- CH2(CH2-C02H) , -NH-C(0)-NH-C(CH2-CH2-C02H)3, -NH-C(0)-NH- CH(CH2-CH2-C02H)2 -NH-C(0)-NH-CH2(CH2-CH2-C02H) , -NH- C (O) -NH-CH2-C (CH2-CH2-C02H) 3, -NH-C (O) -NH-CH2-CH(CH2-CH2- C02H)2, -NH-C(0)-NH-CH2-CH2(CH2-CH2-C02H) , -0-C(0)-NH- C(CH2-CH2-C02H)3, -0-C(0)-NH-CH(CH2-CH2-C02H)2, -O-C(O)- NH-CH2(CH2-CH2-C02H) , -O-C (0) -NH-CH2-C (CH2-CH2-C02H) 3, -O- C(0)-NH-CH2-CH(CH2-CH2-C02H)2, -O-C (O) -NH-CH2-CH2 (CH2-CH2- C02H) , -NH-C(0)-NH-C(CH2-0-CH2-CH2-C02H)3 -NH-C(0)-NH- CH ( CH2-0-CH2CH2C02H) 2 , -NH-C (O) -NH-CH2CH2-0-CH2CH2C02H, -O- C (O) -NH-C (CH2-0-CH2CH2C02H) 3 , -O-C (O) -NH-CH (CH2-0-CH2CH2- C02H) 2 , -0-C (0) -NH-CH2CH2-0-CH2CH2C02H, -NH-C (0) -NH-
CH2CH2-N (CH3 ) 2 , -NH-C ( 0) -N [CH2CH2-N (CH3 ) 2 ] 2 / -NH-C (0) -NH- CH2CH2-N ( CH3 ) -CH2-CH2N ( CH3 ) 2 , -NH-C ( O ) -NH-CH2-CH2-N [ CH2CH2- N(CH3)2]2, -0-C(0)-NH-CH2-CH2-N(CH3)2, -O-C (O) -NH-CH2CH2- N(CH3)CH2CH2N(CH3)2, -O-C (O) -NH-CH2CH2-N[CH2CH2N(CH3) 2] 2 , - NH-C(0)-NH-CH2CH[CH2-N(CH3)2]2/ -O-C (O) -NH-CH2CH [CH2-
N(CH3)2]2, -NH-C(0)-NH-CH2C[CH2-N(CH3)2]3, -0-C(0)-NH- CH2C[CH2-N(CH3)2]3, -NH-C (O) -NH-CH2CH [CH2CH2N(CH3) 2] 2, -O- C (O) -NH-CH2CH [CH2CH2-N (CH3 ) 2] 2 , -NH-C (O) -NH-CH2C [CH2CH2-
N(CH3)2]3, -0-C(0)-NH-CH2C[CH2CH2-N(CH3)2]3, -NH-
C(0)-NHC6H3(C02H)2, -NH-C(0)-NHC6H2(C02H)3, -O-C (O) -NHC6H3- (C02H)2, -0-C(0)-NHC6H2(C02H)3, -NH-C (0) -NHC6H9 (C02H) 2, - NH-C(0)-NHC6H8(C02H)3, -O-C (0) -NHC6H9 (C02H) 2, -O-C(O)-
NHC6H8-(C02H)3, -0-C(0)-NHC6H3(N(CH3)2)2, -O-C(O)-
NHC6H2(N(CH3)2)3, -NH-C(0)-NHC6H9-(N(CH3)2)2/ -NH-C(O)-
NHC6H8(N(CH3)2)3, -0-C(0)-NHC6H9(N(CH3)2)2/ -O-C (O) -NHC6H8- (N(CH3)2)3. In the above groups, a (CH3)2N group can be replaced by a (C2H5)2N group.
Particularly preferred groups are -NH-C (O) -NH-C (CH2-0- CH2CH2C02H)3, -O-C (O) -NH-C (CH2-0-CH2CH2C02H)3, -NH-C(O)- NH-CH2CH2-N[CH2CH2-N(CH3) 2] 2, -NH-C (O) -NH-CH2-NH-CH2CH2- N[CH2CH2-N(CH3)2]2 and -NH-C (O) -N[CH2CH2-N(CH3) 2] 2, where the N(CH3)2 group can be replaced by an N(C2H5)2 group.
Some specific embodiments of the group -C (0) -Xi' -CnH2n- Yi-(R-Y)y are ones as listed above but in which -NH- or -0- is left off at the beginning. Particularly preferred groups are -C(O) -NH-C (CH2-0-CH2CH2C02H) 3, -C (0) -NH-CH2C (CH2-0-CH2CH2C02H) 3, -C (O) -NH-CH2CH2-N[CH2CH2- N(CH3)2]2 and -C (O) -NH-CH2CH2CH2-N[CH2CH2-N(CH3) 2] 2, where the N(CH3)2 group can be replaced by an N(C2H5)2 group.
A preferred subgroup of tertiary diphosphines of the formulae I and la consists of those of the formulae
,
Figure imgf000012_0001
Figure imgf000013_0001
in which Rii and Ri2 are, independently of one another, linear or branched Cι-C4alkylene, and the chain -P-Rn-N-Rι2-P- has from 5 to 8 atoms,
R13 and Ri are identical or different groups selected from among unsubstituted or Cι-Calkyl-, Cι-C4alkoxy- or trifluoromethyl-substituted C5cycloalkyl or C6cycloalkyl and unsubstituted or Cι-C4alkyl-, Cι-Calkoxy-, F-, Cl- or trifluoromethyl-substituted phenyl,
R15 and Rι6 are together C2-C6alkylene,
Ri are, independently of one another, a bond or methylene or ethylidene,
L is a radical of the formula -C(O) -Xi' -CnH2n-Y!- (R-Y)y and
Li is a radical of the formula - [ [Si- (CH3)2]x-CmH2m-Xι-
C(0)-X1'-C„H2„-Y1-(R-Y)y]r, Xi is -0-, -NH- or -NCH3-,
Xi' is -NH- or -N- (Cι-C4alkyl) -; or Xi ' is -0- when Xx is
-NH- or -N-(Cχ-C4alkyl)-, Yi is a direct bond, -0-, -N=, -CH= or |, where
Figure imgf000014_0001
n is from 2 to 4 when
Yi is -O- or -N=,
R is a linear or branched Cι-C8alkane radical which may be uninterrupted or interrupted by -0-, -N= or
-N(CH3)-,
Y is -C02M, -N(CH3)2, -N(CH3)2H+X2 " or -N(CH3) 3 +X2 ", x is 1 and m is 2 or 3 , or x is 0, m is 0 or from 2 to 4, n is 0 or from 2 to 4, r is 1 or 2, y is an integer from 1 to 3 , M is H, Li, Na, K or Ci-C4alkyl, and
X2 is the anion of an inorganic or organic acid.
For X2, the above-described embodiments and preferences apply. X2 can be, for example, an anion selected from the group consisting of chloride, bromide, iodide, hydrogensulfate, dihydrogenphosphate, acetate, benzoate, tosylate and methylsulfonate.
Some specific examples of novel chiral ligands of the formulae I and la are
Figure imgf000015_0001
Figure imgf000015_0002
d HB0)
'(3X) '(H^O-^O^O-O^HOJO-HN-iOO dWθ)
Figure imgf000015_0003
- vτ - 90/00d3/JL3d ιειtO/10 OΛV
Figure imgf000016_0001
Figure imgf000016_0002
and also their Na and K salts and methyl or ethyl esters .
The compounds of the formulae I and la can be prepared in a manner known per se by reacting OH- or NH- functional ditertiary disphosphines with isocyanates or capped isocyanates of a solubilized compound. The invention further provides a process for preparing compounds of the formulae I and la, in which a) OH- or NH-functional ditertiary diphosphines of the formulae III and Ilia,
A-[[Si-(Cι-C4alkyl)2]x-CroH2m-XιH]r (III),
Figure imgf000016_0003
are reacted with a compound of the formula IV,
OCN-C„H2n-Yι-(R-Y)y (IV),
or an activated urea derivative thereof, or b) OH- or NH-functional compounds of the formula IVb,
H-Xι-C„H2n-Y1-(R-Y)y (IVb),
are reacted with a compound of the formula IIlb A- [ [ Si- (Cι-C4alkyl ) 2 ] x-CmH2m-NCO] r ( Illb) ,
or an activated urea derivative thereof, or an activated urea derivative of the compound Ai-H of the formula Ilia, in which A, A1# Xi, Xi ' , Yi, Y, R, x, m, n, y and r are as defined above .
In the case of NH2-functional diphosphines of the formula A- [ [Si- (C1-C4alkyl)2]x-CmH2m-NH2]r, it is also possible to prepare isocyanates of the formula A-[[Si-
(Cι-C4alkyl)2]x-CmH2m-NCO]r or their capped isocyanates first and then to react these with a functional compound of the formula H-Xi-CnH^-Yi- (R-Y)y . In the case of the NH-functional compounds Ai-H of the formula Ilia, it is likewise possible to prepare capped isocyanates and to react these with a functional compound of the formula H-Xι-CnH2n-Yι- (R-Y)y.
Compounds of the formulae III, Ilia, Illb, IVb and IV are known or can be prepared by known or analogous methods. In the preparation, it may be advantageous to use esters (for example methyl or ethyl esters) of carboxylic acids in place of the carboxylic acids (Y is -C02H) and subsequently to obtain the acids and salts by hydrolysis and salt formation.
Activated urea derivatives are also referred to as capped isocyanates. These can, for example, correspond to the formula IVa,
Ri9-(0)C-HN-C„HaB-Yi-(R-Y)y]r (IVa) ,
in which Y, Yx, R, n, y and r are as defined above and R19 is the N-bonded radical of an activating amine. Such amines are essentially cyclic secondary amines, preferably N-heteroaromatics such as pyrrole and in particular imidazole. The compounds of the formulae IV and IVa are obtainable by reaction of appropriate ureas, for example carbonylbisimidazole, with compounds of the formula H2N-CnH2n-Yι- (R-Y)y] r • Here, mixtures of isocyanates and capped isocyanates in chemical equilibrium can be formed and can likewise be used. The reaction is generally carried out at room temperature or slightly elevated temperature in an inert solvent such as toluene. The reaction products can be used directly in further reactions without isolating the isocyanates/capped isocyanates. Syntheses using azolidene are described by H. A. Staab in Angew. Chem. 12, 1962, pages 407 to 419.
The reaction of functional ditertiary diphosphine and isocyanate/capped isocyanate or vice versa is generally carried out in an inert solvent. Examples of suitable solvents are aliphatic, cycloaliphatic or aromatic hydrocarbons, halogenated hydrocarbons, ethers, carboxylic esters, lactones, N-substituted carboxamides, lactams and ketones. The reaction can be carried out at temperatures of from -20 °C to 100 °C.
The compounds of the formulae I and la are very useful ligands for metal complexes, in particular ones which can be used as hydrogenation catalysts and are soluble in polar reaction media such as water or aprotic or protic and polar organic solvents, e.g. alcohols, and can be separated off after the hydrogenation, for example by means of extraction, if appropriate after hydrolysis of ester groups and/or changing the pH.
The invention further provides metal complexes of d8 metals with compounds of the formulae I and la, in particular metal complexes of the formulae V, Va and Vb
A3MeXD (V) , [A3MeX] +E" (Va) , A3Ru ( II ) X3X4 (Vb) ,
in which
A3 is a compound of the formula I or la; X is two monoolefin ligands or one diene ligand; Me is a d8 metal selected from the group consisting of Ir and Rh;
D is -CI, -Br or -I; E is the anion of an oxo acid or complex acid; and
X3 and X4 are identical or different and are as defined for D or E, or X3 and X4 are allyl or 2-methallyl, or X3 is as defined for D or E and X4 is hydride.
Preference is given to metal complexes in which X is 1, 5-hexadiene, 1, 5-cyclooctadiene or norbomadiene . In the metal complexes of the invention, D is -Cl, -Br or -I. In the preferred metal complexes, E" is C10", CF3S03 ", CH3S03 ", HS04 ", BF4 " , B (phenyl)4 ", PF6 ", SbCl6 ", AsF6 " or SbF6 " .
Further possible ruthenium complexes are known from the literature and described, for example, in US 4 691 037, US 4 739 085, US 4 739 084, EP 269395, EP 271310, EP 271311, EP 307168, EP 366390, EP 470756, JP 08081484, JP 08081485, JP 09294932, EP 831099, EP 826694, EP 841343, J. P. Genet, Arcos Organics Acta, 1 (1995) 4, N.C. Zanetti et al . , Organometallics 15 (1996) 860.
The metal complexes of the formulae V, Va and Vb are prepared by methods known from the literature.
The metal complexes of the invention are very useful as catalysts for the hydrogenation of organic double and triple bonds . Examples are compounds containing the groups C=C, C=N, C=0, C=C-N or C=C-0 (cf., for example, K. E. Kδnig, The Applicability of Asymmetric Homogeneous Catalysis, in James D. Morrison (ed.), Asymmetric Synthesis, Vol. 5, Academic Press, 1985). In particular, the metal complexes of the invention are useful for the enantioselective hydrogenation of compounds containing prochiral carbon-carbon and carbon-heteroatom double bonds. Examples of such compounds are prochiral alkenes, imines and ketones. A further aspect of the invention is therefore the use of the novel metal complexes of d8 metals as heterogeneous or homogeneous catalysts for hydrogenation, preferably for the asymmetric hydrogenation of prochiral compounds having carbon- carbon or carbon-heteroatom double bonds in a polar reaction medium. The metal complexes are preferably used for the asymmetric hydrogenation of prochiral compounds having carbon-carbon or carbon-heteroatom double bonds, in particular the Ir complexes for the hydrogenation of prochiral ketimines and the Rh complexes for the hydrogenation of prochiral ketimines and prochiral alkenes .
The invention further provides a process for the hydrogenation of compounds having carbon-carbon or carbon-heteroatom double bonds, which comprises reacting the compounds at a temperature of from -20 to 150 °C with hydrogen in the presence of catalytic amounts of one or more metal complexes of the invention in a polar reaction medium.
The metal complexes of the invention are hydrogenation catalysts or precursors of such catalysts which are activated under the hydrogenation conditions. The metal complexes can be prepared in situ and used as hydrogenation catalysts. The hydrogenations are advantageously carried out under protective gas such as noble gases (argon) .
The process can be carried out under a hydrogen pressure of from 1 to 500 bar, preferably 1-150 bar, particularly preferably from 1 to 120 bar and in particular from 1 to 100 bar.
The reaction temperature can be, for example, from 0 to 150 °C, preferably from 10 to 120 °C and particularly preferably from 30 to 100 °C. The amount of catalyst depends mainly on the desired reaction time and on economic considerations. Higher amounts of catalyst essentially promote shorter reaction times. Catalysts are preferably used in amounts of from 0.0001 to 10 mol%, particularly preferably from 0.001 to 10 mol% and in particular from 0.01 to 5 mol%, based on the compound to be hydrogenated. The molar ratio of substrate to catalyst can be, for example, from 30 to 100000, preferably from 50 to 50000, particularly preferably from 50 to 30000 and in particular from 100 to 2000.
A particularly advantageous aspect is that the hydrogenation can be carried out in polar reaction media, for example polar organic or aqueous media, and in the acid, neutral or basic range, so that reaction conditions optimized for a particular substrate can be set and the catalysts can easily be separated off, for example by means of extraction. If Y in the formulae I and la is an ester group, this can be hydrolyzed beforehand to form the acid group.
For the purposes of the invention, an aqueous reaction medium is one consisting of only water or water in admixture with a water-miscible or water-immiscible organic solvent. The proportion of water is preferably at least 30 per cent by volume, particularly preferably at least 50 per cent by volume and in particular at least 70 per cent by volume. The reaction medium very particularly preferably contains only water. Examples of suitable solvents are alcohols such as methanol, ethanol, propanol, butanol, ethylene glycol and ethylene glycol monomethyl ether; ethers such as diethyl ether, diisobutyl ether, tetrahydrofuran and dioxane; esters and lactones such as ethyl acetate, methyl acetate and valerolactone; sulfoxides and sulfones such as dimethyl sulfoxide, dimethyl sulfone, tetramethylene sulfone; ketones such as acetone or methyl isobutyl ketone; halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloroethane and chlorobenzene; and N-substituted carboxamides and lactarns such as N-methylpyrrolidone and dimethylformamide. If the organic solvents are not miscible with water, a two-phase hydrogenation takes place.
Buffers, bases or acids can be added to the aqueous reaction medium. The reaction can, for example, be carried out at a pH of from 1 to 12, preferably from 2 to 10 and particularly preferably from 3 to 9. Suitable buffers are, in particular, phosphate buffers, but it is also possible to use carboxylic acids, carbonic acid, phosphoric acid and boric acid. Examples of suitable bases are alkali metal hydroxides and alkaline earth metal hydroxides, amines and alkali metal salts of carboxylic acids, carbonic acid, phosphoric acid and boric acid. Examples of suitable acids are HC1, HBr, HI, HBF4, HC104, carboxylic acids (unsubstituted, fluorinated or chlorinated acetic acid, benzoic acid, citric acid) , boric acid, phosphoric acid, methanesulfonic acid, sulfuric acid and carbonic acid. The bases and acids can also be soluble or insoluble polymers such as ion-exchange resins . The amount of bases, acids and/or buffers can be, for example, from 0 to 2, preferably from 0 to 1 and particularly preferably from 0 to 0.5, mol per litre of water.
Examples of suitable organic solvents are esters and lactones such as ethyl acetate and methyl acetate and valerolactone; ketones such as acetone or methyl isobutyl ketone; halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloroethane and chlorobenzene; ethers such as diethyl ether, diisobutyl ether, tetrahydrofuran and dioxane; sulfoxides and sulfones such as dimethyl sulfoxide, dimethyl sulfone, tetramethylene sulfone; N-substituted carboxamides and lactams such as N-methylpyrrolidone and dimethyl- formamide; and particularly alcohols.
For the purposes of the invention, an alcoholic reaction medium means the presence of an alcohol, either alone or in admixture with another organic solvent. Suitable alcohols are aliphatic, cyclo- aliphatic, cycloaliphatic-aliphatic and araliphatic alcohols. Some preferred examples are methanol, ethanol, n- or i-propanol, n-, i- or t-butanol, pentanol, hexanol, cyclohexanol, cyclohexanediol, hydroxymethylcyclohexane or dihydroxymethylcyclohexane, benzyl alcohol, ethylene glycol, diethylene glycol, propanediol, butanediol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, and diethylene glycol monomethyl ether or diethylene glycol monoethyl ether. Preference is given to methanol and ethanol. The proportion of an alcohol is preferably at least 30 per cent by volume, particularly preferably at least 50 per cent by volume and in particular at least 70 per cent by volume. Very particular preference is given to using only an alcohol.
It is known that the catalytic properties of the diphosphine catalysts used can be influenced by addition of cocatalysts, modifiers, metal halides and ammonium halides. It can therefore be advantageous to add alkali metal or ammonium chlorides, bromides or iodides, for example LiCl, LiBr, Lil, Nal, NaBr or tetrabutylammonium iodide, to the reaction mixture. The amount can be, for example, from 0.001 to 5 mol per litre of solvent. Known modifiers are phthalimides and parabanic acid.
The hydrogenation can be carried out continuously or batchwise in various types of reactor. Preference is given to reactors which allow comparatively good mixing and good heat removal, e.g. loop reactors. This type of reactor has been found to be particularly useful when using small amounts of catalyst. The hydrogenated organic compounds which can be prepared according to the invention are active substances or intermediates for preparing such substances, in particular in the production of pharmaceuticals and agrochemicals . Thus, for example, o, o-dialkylarylamine derivatives, in particular those having alkyl and/or alkoxyalkyl groups, act as fungicides, particularly as herbicides. The derivatives can be amine salts, acid amides, e.g. of chloroacetic acid, tertiary amines and ammonium salts (cf., for example, EP-A-0 077 755 and EP-A-0 115 470) .
The following examples illustrate the invention.
A) Preparation of starting compounds
Example Al : Preparation of (C2H502C-CH2CH2-0-CH2- ) 3C-NCO (Al) A solution of 1 mmol of (C2H502C-CH2CH2-0-CH2-) 3C-NH2 (prepared as described by G.R. Newcome et al . , Aldrichimica Acta, 25 (1992) 31-8)] in toluene (7 ml per mmol) is added to an equimolar amount of carbonyldiimidazole and the mixture is stirred overnight. A mixture of isocyanate and imidazolylurea is formed. The solution is used directly for the reactions below.
Example A2 : Preparation of H2N-CH2CH2CH2-N[CH2CH2-N- (C2H5)]2 (A2) a) A mixture of 1 ml (3.5 mmol) of N,N,N',N'- tetraethyldiethylenetriamine in 5 ml of acetonitrile and 938 mg (3.5 mmol) of N- (3-bromopropyl)phthalimide and 977 mg (7 mmol) of potassium carbonate is stirred at room temperature over the weekend. The reaction mixture is extracted with methylene chloride/water, the organic phase is dried over sodium sulfate and evaporated on a rotary evaporator and the crude product is purified by chromatography (silica gel Merck 60, eluant: 50 / 1 mixture of ethanol / triethylamine) . The product is obtained as an oil in a yield of 80%. XH-NMR (CDC13) : 7.9 - 7.83 (m, 2H, phthalimide) , 7.74 - 7.68 (m, 2H, phthalimide), 3.74 (t, 2H, phthalimide- CH2), 2.53 (m, 18H, 9 x CH2-N) , 1.85 (m, 2H, CH2-CH2- CH2), 1.02 (t, 12H, 4 x CH3 ) .
b) 1.52 g (3.79 mmol) of product as described in Example A2a in 10 ml of ethanol are treated with 1 ml of hydrazine hydrate solution and the mixture is stirred under reflux for 1 hour. After cooling to room temperature, 25 ml of methylene chloride are added and the mixture is filtered. The filtrate is evaporated to dryness on a rotary evaporator and the product A2 is dried over solid NaOH. (Yield 97%) . ^-NMR (CDC13) : 2.76 (t, 2H, H2N-CH2-) 2.55 ( , 18H, 9 x CH2-N) , 1.63 (m, 2H, CH2-CH2-CH2) , 1.04 (t, 12H, 4 x CH3) .
B) Preparation of diphosphine ligands Example Bl : Preparation of ligand Kl a) Preparation of the triester
A solution of 377 mg (0.83 mmol) of 2-diphenyl- phosphinomethyl-4-diphenylphosphinopyrrolidine (PPM) in 2.5 ml of toluene is added to a solution prepared as described in Example Al (1.1 mmol of isocyanate triester) and the mixture is stirred overnight. After evaporation on a rotary evaporator and partial removal of the toluene under reduced pressure, the crude product is purified by chromatography (silica gel: Merck 60; eluant: ethyl acetate). 605 mg of product are obtained (yield: 81%) .
b) Preparation of the triacid
1 ml of water and 0.6 g of KOH are added to a solution of 590 mg of the triester prepared as described in Bla in 5 ml of ethanol and the mixture is stirred for 3 hours. The ethanol is then evaporated under reduced pressure and the mixture is dissolved in 25 ml of water. The solution is subsequently acidified using 2N HC1 and extracted a number of times with ethyl acetate. The organic phases are collected, washed with water, dried over sodium sulfate and finally evaporated to dryness under reduced pressure. The product is obtained as a white solid in a yield of 88%.
Example B2 : Preparation of ligand K2 a) Preparation of the triester
The procedure of Example Bla is repeated, except that 3 , 4-diphenylphosphinopyrrolidine (pyrphos) is used as starting compound. The reaction product is obtained in a yield of 63%.
b) Preparation of the triacid The procedure of Example Bib is repeated. The product is obtained as a white solid in a yield of 95%.
Example B3 : Preparation of ligand K3 a) Preparation of the triester The procedure of Example Bla is repeated, except that
2,2' -bis (diphenylphosphino) -5-methyl-5 ' - hydroxymethylbiphenyl (HO-biphemp) is used as starting compound. The reaction product is obtained in a yield of 82%.
b) Preparation of the triacid
The procedure of Example Bib is repeated. The product is obtained as a white solid in a yield of 92%.
Example B4 : Preparation of ligand K4 a) Preparation of the triester
and A, cf .
Figure imgf000026_0001
A solution of 1 g (1.5 mmol) of amine ligand A in 8 ml of methylene chloride is added at 0 °C to an equimolar amount of carbonyldiimidazole in 6 ml of methylene chloride and the reaction mixture is subsequently stirred at room temperature for 2 hours. 1.6 equivalents of H2N-C (CH2-0-CH2CH2C(0) -OCH2CH3 and 5 mg of dibutyltin dilaurate are then added and the mixture is stirred at 50°C for 48 hours. After purification by chromatography (silica gel: Merck 60; eluant: hexane/ethyl acetate, 1:1), the product is obtained as a virtually solid, orange oil in a yield of 65%.
b) Preparation of the triacid: 1 g of diphosphine triester is dissolved in 10 ml of ethanol and treated with 1 ml of 20% aqueous KOH solution. After stirring for 2 hours, the ethanol is evaporated under reduced pressure and the product is dissolved in 20 ml of water. The product is precipitated by addition of 2N HC1, filtered off, washed a number of times with water and finally dried at 50°C in a high vacuum. The product is obtained as an orange-yellow solid in a yield of 92%.
Example B5 : Preparation of ligand K5 a) Preparation of the triester
and B, cf.
Figure imgf000027_0001
A solution of 215 mg (0.34 mmol) of functionalized ligand in 2 ml of methylene chloride is added at 0°C to an equimolar amount of carbonyldiimidazole in 2 ml of methylene chloride and the reaction mixture is subsequently stirred at room temperature for 2 hours . 2 equivalents of amine ligand B and 5 mg of dibutyltin dilaurate are then added and the mixture is stirred at 50°C for 48 hours. After purification by chromatography (silica gel: Merck 60; eluant: hexane/ethyl acetate, 1:1), the product is obtained as a virtually solid, orange oil in a yield of 72%.
b) Preparation of the triacid The procedure of Example B4b is repeated. The orange, solid product is obtained in a yield of 97%.
31P-NMR of the compounds Kl to K5 in CDC13 (Ph = phenyl, xyl = xylyl, cy = cyclohexyl) :
Ligand δ Ligand δ
Kl -7.6, -21.6 Kl -7.96, -21.7
(ester) (acid)
K2 -11.4 K2
(ester) (acid)
K3 -13.6 (d, JPP 35.7 K3 -13.7 (d, JPP 35.2
(ester Hz) (acid) Hz)
-14.5 (d, JPP 35.7 -14.5 (d, JPP 35.2
Hz) Hz)
K4 17.0 (d, JPP 32 K4 16.4 (d, JPP 32
(ester) Hz) Pcy2 (acid) Hz) Pcy2
-25.0 (d JPP 32 -25.5 (d JPP 32
Hz) PPh2 Hz) PPh2
K5 7.3 (d, JPP 19 Hz) K5 6.6 (d, JPP 18 Hz)
(ester) Pxyl2 (acid) Pxyl2
-25.0 (d JPP 19 -24.5 (d JPP 18
Hz) PPh2 Hz) PPh2
1H-NMR: In all cases, the characteristic signals of the ethyl ester group (triplet at δ = 1.2 and quartet at δ = 4.1) have disappeared after saponification of the triester.
Example B6 : Preparation of ligand K6
A solution of 83 mg (0.133 mmol) of the amine ligand B in 1.5 ml of methylene chloride is added at 0 °C to a solution of 22 mg (0.133 mmol) of 1, 1 ' -carbodiimidazole in 2 ml of methylene chloride and the mixture is subsequently stirred at room temperature for 2 hours . 2 equivalents of N,N,N' ,N' -tetraethyldiethylenetriamine and 2 mg of dibutyltin dilaurate are then added and the mixture is stirred overnight . The methylene chloride is subsequently evaporated and the crude product is purified by chromatography (silica gel Merck 60, eluant: 100 / 1 mixture of ethanol / triethylamine) . The product is obtained as an orange, viscous oil in a yield of 87%. ^-NMR (CDC13) : Displays the typical signals for the CH3-CH2-N groups at 1.02 and 2.6.
31P-NMR (CDC13) : + 16.9 (d, Pcy2) , -24.9 (d, PPh2).
Example B7 : Preparation of ligand K7 97 mg (0.335 mmol) of tetraamine A2 in 1.5 ml of methylene chloride are added at 0 °C to a solution of 58 mg (0.35 mmol) of 1, 1 '-carbodiimidazole in 4 ml of methylene chloride and the reaction mixture is subsequently stirred at room temperature for 1 hour. A solution of 154 mg (0.34 mmol) of (2S, 4S) - (- ) -4- diphenylphosphino-2- (diphenylphosphinomethyl) - pyrrolidine in 2 ml of methylene chloride is then added and the mixture is stirred under reflux for 6 hours. Finally, the methylene chloride is evaporated and the crude product is purified by chromatography (silica gel Merck 60, eluant: 25 / 1 mixture of ethanol / triethylamine) . The product is obtained as a viscous colourless oil in a yield of 67%. 1H-NMR (CDCI3) : Displays the typical signals for the CH3-CH2-N groups at 1.02 and 2.55. 31P-NMR (CDCI3): -7.6 (s), -21.5 (s)
c) Use examples Test reaction:
Figure imgf000030_0001
R= H or K, Na: acetamidocinnamic acid (AC)
R= methyl: methyl acetamidocinnamate (MAC)
All operations are carried out under argon as protective gas . The hydrogenations are carried out in a 25 ml glass flask (1 bar of hydrogen pressure) or a 50 ml steel autoclave (>1 bar of hydrogen pressure) provided with magnetic stirrer and a vacuum/gas connection. The hydrogenation solutions are introduced by means of a syringe and needle, in the case of the glass flask through a septum, in the case of the autoclave under a countercurrent of argon. After addition of the hydrogenation solution, the inert gas is displaced by hydrogen (glass apparatus: 4 cycles of vacuum, hydrogen at atmospheric pressure; steel autoclave: 4 cycles of pressurization with 5-10 bar of hydrogen and depressurization) . The hydrogenations are started by switching on the stirrer.
The following phosphate buffers are used: pH 7 = 0.041 mol of Na2HP04 and 0.028 mol of KH2P04/litre; pH 8 = 0.063 mol of Na2HP04 and 0.004 mol of KH2P04/litre .
Conversion and optical yield (enantiomeric excess = ee) are determined on the reaction product using a GC (column: Chirasil-Val) . In the case of hydrogenations of acetamidocinnamic acid, the reaction product is firstly esterified using trimethyloxonium tetrafluoroborate .
Examples C1-C15 :
Method a : Hydrogenation in water
[Rh(norbornadiene) 2]BF4 and the ligand are dissolved in 2 ml of methanol (MeOH) , the solution is stirred for 10 minutes and the MeOH is then evaporated under reduced pressure at 20 - 40°C. In a second vessel, acetamidocinnamic acid is slurried in 5 ml of water, and 2N NaOH is slowly added dropwise until a clear solution is obtained. The phosphate buffer (pH 7) is subsequently added. The pH is checked using pH paper or a pH electrode, and if necessary adjusted to pH 7 by means of 0.1N NaOH or methanesulfonic acid, and the solution is made up to a volume of 10 ml by addition of water. This solution is added to the previously prepared solid catalyst and the mixture is stirred until the catalyst has dissolved (dissolution can be accelerated by means of ultrasound) . The solution obtained is transferred to a hydrogenation apparatus and hydrogenated. Method b: Hydrogenation in water
The ligand is placed in a vessel and dissolved while stirring with the aid of 0. IN NaOH (1 equivalent of NaOH per equivalent of carboxylic acid functions) . After addition of 1 ml of water, the ligand solution is added to [Rh(norbornadiene)2]BF4 and the mixture is stirred until a clear solution is obtained. The substrate solution is prepared as described in Method a, but is made up to 10 ml with water only after addition of the catalyst solution. This solution is transferred to a hydrogenation apparatus and hydrogenated.
Method c : Hydrogenation in water The ligand is placed in a vessel, suspended in 1 ml of water and dissolved by addition of methanesulfonic acid (1% by volume in water) (1 equivalent of methanesulfonic acid per equivalent of amine functions) . The ligand solution is added to [Rh (norbornadiene) 2]BF4 and the mixture is stirred until a clear solution is obtained. The substrate solution is prepared as described in Method a) , but is made up to 10 ml with water only after addition of the catalyst solution. This solution is transferred to a hydrogenation apparatus and hydrogenated.
Method d: Hydrogenation in methanol
[Rh (norbornadiene) 2]BF4 and the ligand are dissolved in 2 ml of MeOH and the solution is stirred for 10 minutes. The substrate, dissolved in 8 ml of MeOH, is added to this catalyst solution. The resulting solution is transferred to a hydrogenation apparatus and hydrogenated.
Example of catalyst separation by extraction:
The hydrogenation solution from Example C9 is, after the hydrogenation, evaporated to dryness under reduced pressure and the mixture is subsequently extracted with ethyl acetate and water (with phosphate buffer, pH 8) . The organic phases are collected, washed with water, dried over sodium sulfate and finally evaporated to dryness on a rotary evaporator. Analysis of the organic product indicates that more than 95% of the rhodium have been separated off.
The reaction conditions are indicated in Table 1. In Examples C5 and C9, MAC is used as substrate, while AC is used in all the others . The hydrogenation in Examples CI and CIO is carried out by Method a) , in Examples C2 to C7 by Method b) , and in Examples C7, C8, Cll, C12 and C15 by Method c) . In Examples C2 to C4 and C7, the hydrogen pressure is 15 bar, in all the other examples 1 bar. In Examples C1-C4, C6, C7 and CIO, the solvent is water; in Examples C8, C9, Cll, C12 and C15 it is methanol; and in Example C5 it is a mixture of 10 ml of water (phosphate buffer pH 8) and 7 ml of ethyl acetate (two-phase hydrogenation) . Reaction temperature: in Examples C1-C5 and C10-C11: 25 °C; in Examples C6 to C9 and C12-C15: 40 °C.
Table 1
Figure imgf000033_0001
Figure imgf000034_0001
The results of the examples listed in Table 1 are shown in Table 2.
Table 2
Figure imgf000034_0002
Examples C16-C23 : Hydrogenation of folic acid 0.0025 mmol of ligand are dissolved in 5 ml of water and 0.5 ml of buffer pH 7 (0.041 mol of Na2HP04 and 0.028 mol of KH2P04 in 1 1 of water) . The carboxylic acid groups of the ligands are then reacted with 0.1N NaOH until a clear solution is formed. The resulting solution is added to 7.4 mg (0.02 mmol) of [Rh(NBD)2]BF and stirred until a solution has formed (NBD is norbornadiene) . This solution is added to a solution of 2 mmol of folic acid disodium salt in 11 ml of water and 1.5 ml of buffer pH 7 and the mixture is transferred to a hydrogenation autoclave provided with a sparging stirrer by means of a syringe in a countercurrent of argon. The autoclave is closed, the argon is replaced by hydrogen and hydrogen is finally injected until the desired pressure has been reached. The hydrogen pressure is maintained by further supplies from the reservoir via a reducing valve. The hydrogenation is started by switching on the stirrer. In the following table, the hydrogenation time reported is the time until the reaction stops (no longer any uptake of hydrogen) . Unless indicated otherwise, this corresponds to complete conversion of the folic acid. The pressure is 80 bar and the reaction temperature is 70 °C (30 °C in Example C21) . The molar ratio of substrate to catalyst (S/C) is 100 in Examples C16-C22 and is 1000 in Example C23. The optical yield DE is reported for the S,S configuration of folic acid. The results are summarized in Table 3.
Table 3 :
Figure imgf000035_0001
Footnotes : 1) Buffer pH 6 : 0.01 mol of Na2HP0 and 0.071 mol of KH2P04 in 1 1 of water; at the end of the reaction, another 4 ml of IN KH2P04 are added.
2) 5 mmol of folic acid disodium salt, 0.005 mmol of i [Rh(NBD)2]BF4 and 0.00675 mmol of ligand are used in a total of 16 ml of water and 2 ml of buffer pH 7.

Claims

WHAT IS CLAIMED IS:
1. A compound of the formula I or la,
A- [ [Si- (Cι-C4alkyl) 2]x-CmH2m-Xι-C (0) -Xi ' -
CnH2n-Yι-(R-Y)y]r (I),
Aι-C(0)-X1'-CnH2n-Yι-(R-Y)y (la) ,
in which
A is a monovalent to tetravalent framework of a ditertiary diphosphine bound via a C atom, Ai is a monovalent framework of a 3-8-membered N- heterocyclic ditertiary diphosphine bound via the N atom,
Xi is -0-, -NH- or -N- (Cι-C4alkyl) -,
Xi' is -NH- or -N- (Cι-C4alkyl) - ; or i ' is -O- when
Xi is -NH- or -N- (Cι-C4alkyl) -,
Yi is a direct bond, -0-, -N=, -CH=, , a
Figure imgf000037_0001
(y+l)-valent benzene radical, or a (y+l)-valent radical of a 3-8-membered cycloalkane, where n is from 1 to 4 when Yi is -O- or -N=,
R is a linear or branched, (y+D-valent radical of a Cι-Cι2alkane which may be uninterrupted or interrupted by -0-, -N= or -N(Cι-C4alkyl) -, or
R is a direct bond and Yi is not -O- or -N=,
Y is -C02M, -NtCi-Cialkyl -, -N(Cι-C4alkyl) 2H+X2 " or
-N(Cι-Calkyl)3 +X2 ", x is 1 and m is from 2 to 4, or x is 0, m is 0 or an integer from 1 to 4, n is 0 or an integer from 1 to 4, r is an integer from 1 to 4, y is an integer from 1 to 5,
M is H, an alkali metal or a monovalent hydrocarbon radical having from 1 to 18 C atoms, and
X2 is the anion of an inorganic or organic acid.
2. A compound according to claim 1, wherein the two phosphine groups of the ditertiary diphosphines contain two identical or different radicals selected from the group consisting of linear or branched Cι-Cι2alkyl; unsubstituted or Cι-C6alkyl- or Cι-C6alkoxy-substituted C5-Cι2cycloalkyl or C5-Cι2cycloalkyl-CH2-; phenyl and benzyl; and phenyl and benzyl substituted by halogen, Cι-C6alkyl, Ci- Cehaloalkyl, Cι-C6alkoxy, Cι-C6haloalkoxy, (C6- H5)3Si, (Cι-Cι2alkyl)3Si or -C02-Cι-C6alkyl ; or the phosphine groups contain unsubstituted or halogen- , Cι-C6alkyl- or d-C6alkoxy-substituted dimethylene, trimethylene, tetramethylene, pentamethylene or 3-oxapentane-l, 5-diyl .
3. A compound according to claim 1, wherein the tertiary diphosphines are ones in which the phosphine groups are bound (a) to different C atoms of a chain having from 2 to 6 atoms or (b) directly or via a bridging group -CRaRb- either in the ortho positions of a cyclopentadienyl ring or each to a cyclopentadienyl ring of a ferrocenyl group, where Ra and Rb are identical or different and are H, Cι-C8alkyl, Cι-C4fluoroalkyl, C5-C6cycloalkyl, phenyl, benzyl or Cι-C4alkyl- or Cι-C4alkoxy-monosubstituted to -trisubstituted phenyl or benzyl .
4. A compound according to claim 1, wherein the diphosphine radicals A and Ai in the formulae I and la correspond to the formulae II, Ila and lib,
RJRJP R,—P 4R, ('')' - 33 -
Figure imgf000039_0001
N (lib).
in which
Ri, R2, R and R5 are each, independently of one another, a hydrocarbon radical having from 1 to 20 C atoms which is unsubstituted or substituted by halogen, Cι-C6alkyl, Cι-C6haloalkyl, Cι-C6alkoxy, Ci- Cehaloalkoxy, (C6H5)3Si, (Cι-Cι2alkyl) 3Si or -C02-Cι- C6alkyl; or Ri and R2 or R4 and R5 are in each case together unsubstituted or halogen-, Cι-C6alkyl- or Cι-C6alkoxy-substituted tetramethylene, pentamethylene or 3-oxapentane-l, 5-diyl; and R3 is unsubstituted or Cι-C6alkyl-, Cι-C6alkoxy-, C5cycloalkyl- or C6cycloalkyl-, phenyl-, naphthyl- or benzyl-substituted C2-C4alkylene; unsubstituted or Cι-C6alkyl-, phenyl- or benzyl-substituted 1,2- or 1, 3-cycloalkylene, 1,2- or 1, 3-cycloalkenylene, 1,2- or 1, 3-bicycloalkylene or 1,2- or 1,3- bicycloalkenylene having from 4 to 10 C atoms; unsubstituted or Cι-C6alkyl-, phenyl- or benzyl- substituted 1,2- or 1, 3-cycloalkylene, 1,2- or 1, 3-cycloalkenylene, 1,2- or 1, 3-bicycloalkylene or 1,2- or 1, 3-bicycloalkenylene having from 4 to 10 C atoms to which methylene or C2-C4alkylidene is bound in the 1 and/or 2 positions or in the 3 position; 1,4-butylene which is substituted by R6R7C(0-)2 in the 2,3 positions and is unsubstituted or substituted by Cι-C6alkyl, phenyl or benzyl in the 1 and/or 4 positions, where R6 and R7 are, independently of one another, hydrogen, Cι-C6alkyl, phenyl or benzyl; 3,4- or 2, 4-pyrrolidinylene or methylene-4-pyrrolidin-4-yl whose N atom is substituted by hydrogen, Cι-Cι2alkyl, phenyl, benzyl, Cι-Cι2alkoxycarbonyl, Cι-C8acyl, Cι-Cι2alkylaminocarbonyl; or unsubstituted or halogen-, -OH-, Cι-C6alkyl-,
Cι-C6alkoxy-, phenyl-, benzyl-, phenyloxy- or benzyloxy-substituted 1, 2 -phenyl ene, 2-benzylene, 1,2-xylylene, 1, 8-naphthylene, 2 , 2 ' -binaphthylene or 2 , 2 ' -biphenylene ; or R3 is a radical of the formulae
Figure imgf000040_0001
in which R8 is hydrogen, Cι-C8alkyl,
Cι-C4f luoroalkyl, unsubstituted phenyl or phenyl substituted by from 1 to 3 F, CI, Br, C!-C4alkyl,
Cι-C4alkoxy or fluoromethyl substituents; q in formula Ila is 0 or an integer from 1 to 6, where the radical of the formula Ila is unfused or fused with cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic radicals, and the radical of the formula Ila is unsubstituted or substituted by halogen, Cι-C6alkyl, Cι-C6haloalkyl, Cι-C6alkoxy, Cι-C6haloalkoxy, (C6H5)3Si,
(Cι-Cι2alkyl)3Si or -C02-Ci-C6alkyl; and R9 and Rι0 are, independently of one another,
Cι-Calkylene .
5. A compound according to claim 1, wherein the group -Xι-C(0)-NH-CnH2n-Yι-(R-Y)y in formula I is -NH- C(0)-NH-C(CH2-0-CH2CH2C02H)3, -O-C (O) -NH-C (CH2-0-
CH2CH2C02H) 3 , -NH-C ( O) -NH-CH2CH2-N [CH2CH2-N ( CH3 ) 2 ] 2 , -NH-C(0)-NH-CH2CH2CH2-N[CH2CH2-N(CH3)2]2 or -NH-C(O)- N[CH2CH2-N(CH3)2]2, where the N(CH3)2 group may be replaced by an N(C2H5)2 group; and the group -C (O) -NH-CnH2n-Yι- (R-Y)y in formula la is -C(0)-NH-C(CH2-0-CH2CH2C02H)3, -C (O) -NH-CH2C (CH2-0-
CH2CH2C02H) 3 , -C (0) -NH-CH2CH2N [CH2CH2-N (CH3 ) 2] 2 ,
-C(0)-NH-CH2CH2CH2-N[CH2CH2-N(CH3)2]2 or -C(0)-NH- CH2CH2CH2-N[CH2CH2-N(CH3)2]2, where the N(CH3)2 group may be replaced by an N(C2H5)2 group.
A compound of the formula I or la according to claim 1 which has one of the following formulae:
Figure imgf000041_0001
Figure imgf000041_0002
Figure imgf000041_0003
in which
Rn and Ri2 are, independently of one another, linear or branched Cι-C4alkylene, and the chain -P-
Rn-N-Rι2-P- has from 5 to 8 atoms, Ri3 and Ri4 are identical or different groups selected from among unsubstituted or Cι-Calkyl-,
Cι-C4alkoxy- or trifluoromethyl-substituted
C5cycloalkyl or C6cycloalkyl and unsubstituted or
Cι-C4alkyl-, Cι-Calkoxy-; F-, CI- or trifluoromethyl-substituted phenyl,
R15 and Ri6 are together C2-C6alkylene,
R17 are, independently of one another, a bond or methylene or ethylidene,
L is a radical of the formula -C(O) -Xi ' -CnH2n-Yι- (R- Y)y and
Li is a radical of the formula - [ [Si- (CH3) 2]x-CmH2m-
Xi-C (O) -Xi ' -CnH2n-Y!- (R-Y)y] r,
Xi is -0-, -NH- or -NCH3-,
Xi' is -NH- or -N- (Cι-C4alkyl) -; or Xi ' is -O- when Xi is -NH- or -N- (Cι-C4alkyl) -,
Yi is a direct bond, -0-, -N=, -CH= or
Figure imgf000042_0001
where n is from 2 to 4 when
Figure imgf000042_0002
R is a linear or branched Cι-C8alkane radical which may be uninterrupted or interrupted by -0-, -N= or
-N(CH3)-,
Y is -C02M, -N(CH3)2, -N(CH3)2H+X2- or -N(CH3) 3 +X2 ", x is 1 and m is 2 or 3 , or x is 0, m is 0 or from 2 to 4, n is 0 or from 2 to 4, r is 1 or 2, y is an integer from 1 to 3, M is H, Li, Na, K or Cι-C4alkyl, and
X2 is the anion of an inorganic or organic acid.
7. A metal complex of a d8 metal with a compound of the formula I or la.
8. A metal complex according to claim 7 which has the formula V, Va or Vb,
A3MeXD (V), [A3MeX]+E~ (Va) , A3Ru(II)X3X4 (Vb) ,
in which A3 is a compound of the formula I or la;
X is two monoolefin ligands or one diene ligand;
Me is a d8 metal selected from the group consisting of Ir and Rh;
D is -CI, -Br or -I; E is the anion of an oxo acid or complex acid; and
X3 and X4 are identical or different and are as defined for D or E, or X3 and X4 are allyl or 2- methallyl, or X3 is as defined for D or E and X4 is hydride .
9. A process for the hydrogenation of compounds having carbon-carbon or carbon-heteroatom double bonds, which comprises reacting the compounds at a temperature of from -20 to 150 °C with hydrogen in the presence of catalytic amounts of one or more metal complexes according to claim 8 in a polar reaction medium.
10. The use of a metal complex of a d8 metal according to claim 8 as a heterogeneous or homogeneous catalyst for hydrogenation, preferably for the asymmetric hydrogenation of prochiral compounds having carbon-carbon or carbon-heteroatom double bonds, in a polar reaction medium.
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