EP1194437A1 - Ligands de diphosphine pour complexes metalliques - Google Patents

Ligands de diphosphine pour complexes metalliques

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Publication number
EP1194437A1
EP1194437A1 EP00945913A EP00945913A EP1194437A1 EP 1194437 A1 EP1194437 A1 EP 1194437A1 EP 00945913 A EP00945913 A EP 00945913A EP 00945913 A EP00945913 A EP 00945913A EP 1194437 A1 EP1194437 A1 EP 1194437A1
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Prior art keywords
alkyl
substituted
phenyl
unsubstituted
alkoxy
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EP00945913A
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German (de)
English (en)
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Benoít Pugin
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Solvias AG
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Solvias AG
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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 System
    • 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

Des diphosphines ditertiaires, chirales ou non chirales, présentant des substituants solubilisants, par exemple, -NH-C(O)-NH-C(CH2-O-CH2CH2CO2H)3, dans le squelette de la diphosphine, constituent d'excellents ligands pour des complexes métalliques d8 qui sont solubles dans des milieux polaires, par exemple, eau ou alcools, et qui peuvent être utilisés comme catalyseurs d'hydrogénation asymétriques ou symétriques pour des composés ayant des doubles liaisons carbone-carbone ou carbone-hétéroatome.
EP00945913A 1999-07-14 2000-07-12 Ligands de diphosphine pour complexes metalliques Ceased EP1194437A1 (fr)

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DE3818435A1 (de) * 1988-02-19 1989-08-31 Hoechst Ag Optisch aktive rhodiumkomplexe von 3,4-bis(diarylphosphino)-pyrrolidinen und ihre verwendung zur herstellung von phosphinothricin durch asymmetrische hydrierung
DE59201991D1 (de) * 1991-01-25 1995-06-01 Ciba Geigy Ag Silangruppen enthaltende Diphosphine, immobilisierte Diphosphine und deren Verwendung als Hydrierkatalysatoren.
DK0512416T3 (da) * 1991-05-03 1997-06-30 Hoechst Ag Nye homochirale diphosfiner
EP0729969B1 (fr) * 1995-02-24 2000-08-16 Novartis AG Ligandes ferrocène-disphosphine silylée, support inorganique ou à base de polymères organiques les contenant et leurs complexes métalliques et procédé de préparation et utilisation
HRP960295A2 (en) * 1995-07-06 1997-08-31 Ciba Geigy Ag Process for the hydrogenation of imines in the presence of immobilized iridium-diphosphine catalysts
WO1998001457A1 (fr) * 1996-07-10 1998-01-15 Novartis Ag Ferrocenyldiphosphines fonctionnalisees, procede pour leur preparation et leur utilisation

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