EP1807437A1 - Ligands for use in asymmetric hydroformylation - Google Patents

Ligands for use in asymmetric hydroformylation

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Publication number
EP1807437A1
EP1807437A1 EP05799685A EP05799685A EP1807437A1 EP 1807437 A1 EP1807437 A1 EP 1807437A1 EP 05799685 A EP05799685 A EP 05799685A EP 05799685 A EP05799685 A EP 05799685A EP 1807437 A1 EP1807437 A1 EP 1807437A1
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EP
European Patent Office
Prior art keywords
alkyl
aryl
cycloalkyl
hydrogen
chiral
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP05799685A
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German (de)
French (fr)
Inventor
Wolfgang Ahlers
Martina Egen
Martin Volland
Christoph JÄKEL
Frank Hettche
Rocco Paciello
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
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Publication date
Application filed by BASF SE filed Critical BASF SE
Publication of EP1807437A1 publication Critical patent/EP1807437A1/en
Withdrawn legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
    • B01J31/185—Phosphites ((RO)3P), their isomeric phosphonates (R(RO)2P=O) and RO-substitution derivatives thereof
    • B01J31/1855—Triamide derivatives thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
    • B01J31/185—Phosphites ((RO)3P), their isomeric phosphonates (R(RO)2P=O) and RO-substitution derivatives thereof
    • B01J31/186—Mono- or diamide derivatives thereof
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    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2495—Ligands comprising a phosphine-P atom and one or more further complexing phosphorus atoms covered by groups B01J31/1845 - B01J31/1885, e.g. phosphine/phosphinate or phospholyl/phosphonate ligands
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    • C07—ORGANIC CHEMISTRY
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    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/49—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide
    • C07C45/50—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide by oxo-reactions
    • C07C45/505—Asymmetric hydroformylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
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    • 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
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    • 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
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    • 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
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    • C07F9/572—Five-membered rings
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    • 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
    • C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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    • 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
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65848—Cyclic amide derivatives of acids of phosphorus, in which two nitrogen atoms belong to the ring
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    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B01J2231/321—Hydroformylation, metalformylation, carbonylation or hydroaminomethylation
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    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B01J2231/323—Hydrometalation, e.g. bor-, alumin-, silyl-, zirconation or analoguous reactions like carbometalation, hydrocarbation
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    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B01J2231/324—Cyclisations via conversion of C-C multiple to single or less multiple bonds, e.g. cycloadditions
    • B01J2231/325—Cyclopropanations
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    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B01J2231/324—Cyclisations via conversion of C-C multiple to single or less multiple bonds, e.g. cycloadditions
    • B01J2231/326—Diels-Alder or other [4+2] cycloadditions, e.g. hetero-analogues
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    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
    • B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations
    • B01J2231/342—Aldol type reactions, i.e. nucleophilic addition of C-H acidic compounds, their R3Si- or metal complex analogues, to aldehydes or ketones
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    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/44—Allylic alkylation, amination, alkoxylation or analogues
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    • B01J2231/52—Isomerisation reactions
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    • B01J2231/54—Metathesis reactions, e.g. olefin metathesis
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    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
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Definitions

  • the present invention relates to chiral phosphorochelate compounds, catalysts containing such a compound as ligands and to asymmetric synthesis in the presence of such a catalyst.
  • Asymmetric synthesis is the term for reactions in which a chiral moiety is generated from a chiral moiety, resulting in unequal amounts of stereoisomeric products (enantiomers or diastereomers).
  • the asymmetric synthesis has gained immense importance, above all in the pharmaceutical industry, since frequently only a certain optically active isomer is therapeutically active.
  • the synthesis should lead to the desired isomer in high optical purity and in high chemical yield.
  • Hydroformylation or oxo synthesis is an important industrial process and serves to prepare aldehydes from olefins, carbon monoxide and hydrogen. These aldehydes may optionally be hydrogenated in the same operation with hydrogen to the corresponding oxo alcohols.
  • the asymmetric hydroformylation is an important method for the synthesis of chiral aldehydes and is of interest as access to chiral building blocks for the preparation of flavorings, cosmetics, plant protection agents and pharmaceuticals.
  • the hydroformylation reaction itself is highly exothermic and generally runs under elevated pressure and at elevated temperatures in the presence of catalysts.
  • the catalysts used are Co, Rh, Ir, Ru, Pd or Pt compounds or complexes which modify the activity and / or selectivity of N, P, As or Sb-containing ligands - can be decorated.
  • olefins having more than two carbon atoms it may come to the formation of mixtures of isomeric aldehydes due to the possible CO addition to each of the two carbon atoms of a double bond.
  • the use of olefins having at least four carbon atoms by double bond isomerization may lead to the formation of mixtures of isomeric olefins and optionally also of isomeric aldehydes.
  • phosphorus-containing ligands in the rhodium-low-pressure hydroformylation for stabilizing and / or activating the catalyst metal.
  • Suitable phosphorus ligands are z.
  • phosphines, phosphinites, phosphonites, phosphites, phosphoramidites, phospholes and phosphabenzenes are z.
  • the currently most widely used ligands are triarylphosphines, such as.
  • triphenylphosphine and sulfonated triphenylphosphine since they have sufficient stability under the reaction conditions.
  • WO 00/56451 describes hydroformylation catalysts based on phosphinamidite ligands, in which the phosphorus atom, together with an oxygen atom to which it is bonded, represents a 5- to 8-membered heterocycle.
  • WO 02/083695 describes pnicogen chelate compounds in which at least one pyrrole group is bonded to each of the pnicogen atoms via the pyrrole nitrogen atom. These pnicogen chelate compounds are useful as ligands for hydroformylation catalysts.
  • WO 03/018192 describes, inter alia, pyrrole phosphorus compounds in which at least one substituted and / or pyrrole group integrated into a fused ring system is covalently linked via its pyrrolic nitrogen atom to the phosphorus atom, which has very good stability when used as ligands in hydroformylation catalysts distinguished.
  • DE-A-103 42 760 describes pnicogen compounds which have two pnicogen atoms, pyrrole groups being able to be bound to both pnicogen atoms via a pyrrolic nitrogen atom and both pnicogen atoms being bound to a bridging group via a methylene group. These pnicogen compounds are useful as ligands for hydroformylation catalysts.
  • EP-AO 503 884 describes an optically active 2'-substituted 2'-diphenylphosphine-1, 1 '-binaphthyl compound, catalysts based on Koch ⁇ transition metal complexes having such a compound as ligands and a method for enantioselective Silylation using such a catalyst.
  • EP-A-0 614 870 describes a process for the preparation of optically active aldehydes by hydroformylation of prochiral 1-olefins in the presence of a rhodium complex as hydroformylation catalyst which has an asymmetrical phosphorus-containing ligand with 1, 1 ' -binaphthylene backbone.
  • the preparation of the unbalanced phosphorus atom-containing ligands is associated with high synthetic effort.
  • EP-A-0 614 901, EP-A-0 614 902, EP-A-0 614 903, EP-A-0 684 249 and DE-A-198 53 748 describe unbalanced phosphorus atom-containing ligands of comparable structure.
  • WO 93/03839 (EP-B-0 600 020) describes an optically active metal-ligand complex catalyst comprising an optically active pnicogen compound as ligand and processes for asymmetric synthesis in the presence of such a catalyst.
  • the unpublished German patent application P 103 55 066.6 relates to a process for asymmetric synthesis in the presence of a chiral catalyst, comprising at least one complex of a metal of VIII. Subgroup with ligands capable of dimerization via non-covalent bonds, such catalysts and their use.
  • the object of the present invention is to provide chiral compounds and catalysts based thereon which are suitable for the preparation of chiral compounds with high stereoselectivity and high reactivity. These catalysts should be particularly suitable for the hydroformylation of olefins with good stereoselectivity and high reactivity.
  • R a and R 8 independently of one another represent 5- to 7-membered heterocyclic groups which are bonded to the phosphorus atom via a ring nitrogen atom or
  • R ⁇ and R ⁇ together with the phosphorus atom to which they are attached, stand for a 5- to 7-membered heterocycle which additionally has an optionally substituted nitrogen atom and a further heteroatom selected from oxygen and optionally substituted nitrogen, both bound directly to the phosphorus atom,
  • R Y and R ⁇ independently of one another are alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where the alkyl radicals have 1, 2, 3, 4 or 5 substituents selected from cycloalkyl, heterocycloalkyl, aryl, hetaryl, alkoxy, cycloalkoxy, heterocycloalkoxy , Aryloxy, hetaryloxy, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine,
  • E 1 , E 2 and E 3 are each the same or different radicals selected under hydrogen, alkyl, cycloalkyl, or aryl and X 'is an anion equivalent,
  • cycloalkyl, heterocycloalkyl, aryl and hetaryl radicals R v and R ⁇ may have 1, 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents previously mentioned for the alkyl radicals R Y and R ⁇ , or
  • X ⁇ is O, S, SiR ⁇ R or NR ⁇ , where R ⁇ , R ⁇ and ⁇ R is independently hydrogen, are alkyl, Cycioalkyl, heterocycloalkyl aryl or hetaryl, and Y stands for a chiral divalent bridging group.
  • Chiral compounds in the context of the present invention are compounds having at least one chiral center (that is to say at least one asymmetric atom, in particular at least one asymmetric C atom or P atom), with chirality axis, chirality plane or helical turn.
  • chiral catalyst is widely understood in the context of the present invention. It comprises both catalysts which have at least one chiral ligand and also catalysts with intrinsically achiral ligands which, owing to the arrangement of the ligands as a result of noncovalent interactions and / or the arrangement of the ligands in complexed form, have center chirality, axial chirality , planar chirality or helicity.
  • a “prochiral compound” is understood to mean a compound having at least one prochiral center.
  • “Asymmetric synthesis” refers to a reaction in which a compound having at least one prochiral center is formed from a compound having at least one center of chirality, a chirality axis, a plane of chirality, or a helical coil, whereby the stereoisomeric products are formed in uneven amounts.
  • Steps are compounds of the same constitution but with different atomic arrangements in three-dimensional space.
  • Enantiomers are stereoisomers which behave in mirror-image relationship to one another.
  • R and S are the descriptors of the CIP system for the two
  • Enantiomers and represent the absolute configuration of the asymmetric atom.
  • the process of the invention results in products that are enriched in a particular stereoisomer.
  • the achieved "enantiomeric excess” (ee) is generally at least 20%, preferably at least 50%, in particular at least 80%.
  • alkyl includes straight-chain and branched alkyl groups. Preferably, it is straight-chain or branched C 1 -C 20 -alkyl, preferably CrCl 2 -AIkVl-, particularly preferably C 1 -C 8 -AIkVl- and most preferably C r C 4 alkyl groups.
  • alkyl groups are in particular methyl, ethyl, propyl, isopropyl, n-butyl, 2-butyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methylbutyl, 3-methylbutyl, 1, 2 -Dimethylpropyl, 1, 1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 2-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl , 2,3-dimethylbutyl, 1, 1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1, 1, 2-trimethylpropyl,
  • alkyl also includes substituted alkyl groups which are generally 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent aus ⁇ selected from the groups cycloalkyl, aryl, hetaryl, halogen, NE 1 E 2 , NE 1 E 2 E 3+ , COOH, carboxylate, -SO 3 H and sulfonate.
  • alkylene in the context of the present invention stands for straight-chain or branched alkanediyl groups having 1 to 4 carbon atoms.
  • cycloalkyl in the context of the present invention comprises unsubstituted as well as substituted cycloalkyl groups, preferably C 5 -C 7 -cycloalkyl groups, such as cyclopentyl, cyclohexyl or cycloheptyl, which in the case of a substitution, in general 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent selected from the groups alkyl, alkoxy and halogen, can carry.
  • substituted cycloalkyl groups preferably C 5 -C 7 -cycloalkyl groups, such as cyclopentyl, cyclohexyl or cycloheptyl, which in the case of a substitution, in general 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent selected from the groups alkyl, alkoxy and halogen, can carry.
  • heterocycloalkyl in the context of the present invention comprises saturated, cycloaliphatic groups having generally 4 to 7, preferably 5 or 6, ring atoms in which 1 or 2 of the ring carbon atoms are selected by heteroatoms, preferably selected from the elements oxygen, nitrogen and sulfur, are substituted and which may optionally be substituted, wherein in the case of a substitution, these heterocycloaliphatic groups 1, 2 or 3, preferably 1 or 2, particularly preferably 1 substituent selected from alkyl, aryl, COOR f , COO " M + and NE 1 e 2, preferably alkyl, can carry.
  • heterocycloaliphatic Grup ⁇ examples are groups pyrrolidinyl, piperidinyl, 2,2,6,6-tetramethyl piperidinyl, imidazolidinyl, pyramidal zolidinyl, oxazolidinyl, Morpholidinyl, thiazolidinyl, isothiazolidinyl, isoxazolidinyl, Piperazinyl, tetrahydrothiophenyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl.
  • aryl for the purposes of the present invention includes unsubstituted as well as substituted aryl groups, and is preferably phenyl, ToIyI, XyIyI, mesityl, naphthyl, fluorenyl, anthracenyl, phenanthrenyl or naphthacenyl, more preferably phenyl or naphthyl, said Aryl groups in the case of a substitution in general 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent selected from the groups alkyl, alkoxy, carboxyl, carboxylate, trifluoromethyl, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , nitro, cyano or halogen.
  • heterocycloaromatic groups preferably the groups pyridyl, quinolinyl, acridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and the subgroup of the "pyrrole group", these heterocycloaromatic groups in the case of Substitu tion generally 1, 2 or 3 substituents selected from the groups alkyl, alkoxy, carboxyl, carboxylate, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , trifluoromethyl or halogen, can carry.
  • pyrrole group in the context of the present invention is a series of unsubstituted or substituted heterocycloaromatic groups which are structurally derived from the pyrrole skeleton and contain a pyrrole nitrogen atom in the heterocycle which is covalently linked to other atoms, for example a pnicogen atom can be.
  • pyrrole group thus includes the unsubstituted or substituted groups pyrrolyl, imidazolyl, pyrazolyl, indolyl, purinyl, indazolyl, benzotriazolyl, 1, 2,3-triazolyl, 1, 3,4-triazolyl and carbazolyl, which in the case of Substitution in general 1, 2 or 3, preferably 1 or 2, particularly preferably 1 substituent selected from the groups alkyl, alkoxy, acyl, carboxyl, carboxylate, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , trifluoromethyl or halogen, tra ⁇ gene can.
  • a preferred substituted indolyl group is the 3-methylindolyl group.
  • bispyrrole group for the purposes of the present invention includes divalent groups of the formula
  • the bispyrrole groups may also be unsubstituted or substituted and in the case of a substitution per pyrrole group unit generally 1, 2 or 3, preferably 1 or 2, in particular 1 substituent selected from alkyl, alkoxy, carboxyl, carboxylate, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , trifluoromethyl or halogen carry, wherein in these statements to the number of possible substituents linking the Pyrrol weaknessein- units by direct chemical bonding or by means of the genann ⁇ th groups mentioned above mediated linking is not considered a substitution.
  • Carboxylate and sulfonate in the context of this invention preferably represent a derivative of a carboxylic acid function or a sulfonic acid function, in particular a metal carboxylate or sulfonate, a carboxylic acid or sulfonic acid ester function or a carboxylic acid or sulfonic acid amide function.
  • these include z.
  • esters with CrC 4 alkanols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol and tert-butanol. These include the primary amides and their N-alkyl and NN-dialkyl derivatives.
  • acyl in the context of the present invention represents alkanoyl or aroyl groups having generally 2 to 11, preferably 2 to 8, carbon atoms, for example, the acetyl, propanoyl, butanoyl, pentanoyl, hexanoyl, heptanoyl, 2-ethylhexanoyl, 2-propylheptanoyl, benzoyl or naphthoyl group.
  • the groups NE 1 E 2 , NE 4 E 5 , NE 7 E 8 , NE 10 E 11 , NE 13 E 14 , NE 16 E 17 and NE 19 E 20 are preferably N, N-dimethylamino, N, N-diethylamino , N, N-dipropylamino, N, N-diisopropylamino, N, N-di-n-butylamino, N, N-di-t-butylamino, N, N-dicyclohexylamino or N, N-diphenylamino.
  • Halogen is fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine and bromine.
  • M + represents a cation equivalent, ie a monovalent cation or the proportion of a polyvalent cation corresponding to a positive single charge.
  • the cation M + serves only as a counterion to the neutralization of negatively charged substituent groups, such as the COO or the sulfonate group, and can in principle be chosen arbitrarily. Preference is therefore given to alkali metal, in particular Na + , K + , Li + ions or onium ions, such as ammonium, mono-, di-, tri-, tetraalkylammonium, phosphonium, tetraalkylphosphonium or tetraarylphosphonium ions used.
  • anion equivalent X ' which serves merely as a counterion of positively charged substituent groups, such as the ammonium groups, and can be chosen arbitrarily from monovalent anions and the portions of a polyvalent anion corresponding to a negative single charge.
  • Suitable anions are z.
  • halide ion X ' such as chloride and bromide.
  • Preferred anions are sulfate and sulfonate, e.g. As SO 4 2 " , tosylate, trifluoromethanesulfonate and methyl sulfonate.
  • the values of x represent an integer of 1 to 240, preferably an integer of 3 to 120.
  • Condensed ring systems may be fused (fused) aromatic, hydroaromatic and cyclic compounds.
  • Condensed ring systems consist of two, three or more than three rings.
  • ortho-fusing d. H. each ring has one edge or two atoms in common with each adjacent ring, and a peri-annulation in which one carbon atom belongs to more than two rings.
  • Preferred among the fused ring systems are ortho-fused ring systems.
  • the substituents R ⁇ and R ⁇ are heteroatom-containing groups which are bonded to the phosphorus atom via an optionally substituted nitrogen atom are where R ⁇ and R p are not connected to each other.
  • R ⁇ and R p are not connected to each other.
  • Aik is a C r C 4 alkyl group
  • R a, R b, R c and R d are independently hydrogen, CrC 4 alkyl, Ci-C 4 alkoxy, acyl, halogen, trifluoromethyl, dC 4 alkoxycarbonyl or carboxyl.
  • At least one of the radicals R ⁇ and R ⁇ is an unsubstituted or substituted indolyl group which is in particular selected from groups II. E to II. I.
  • the radicals R a and R b are preferably independently of one another selected from hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and halogen. If at least one of the radicals R a and R b is C 1 -C 4 -alkyl, then especially methyl, ethyl, n-propyl, isopropyl or tert-butyl. If at least one of the radicals R a and R b is C 1 -C 4 -alkoxy, then especially methoxy, ethoxy, n-propyloxy, isopropyloxy or tert-butyloxy. If at least one of R a and R b is halogen, then especially chlorine.
  • the radicals R a and R b are both hydrogen.
  • one of the radicals R a and R b is hydrogen and the other is a radical other than hydrogen, especially methyl, methoxy or chlorine.
  • the radical other than hydrogen is then preferably in the 4-, 5- or 6-position of the indole skeleton.
  • both radicals R ⁇ and R ⁇ stand for such an unsubstituted or substituted indolyl group.
  • R ⁇ and R ⁇ stand for such an unsubstituted or substituted indolyl group.
  • some advantageous pyrrol groups are listed below:
  • the 3-methylindolyl group (skatolyl group) of the formula II.f1 is particularly advantageous.
  • Hydroformylation catalysts based on ligands which have one or more 3-methylindolyl group (s) attached to the phosphorus atom are distinguished by particularly high stability and thus particularly long catalyst residence times.
  • phosphorus chelate compounds in which the radicals R ⁇ and R ⁇ are selected independently of one another below:
  • FT and R ß together with the phosphorus atom to which they are attached for a 5- to 7-membered heterocycle having two bonded to the phosphorus ring heteroatom me, wherein it is at least one of these ring heteroatoms is an optionally substituted nitrogen atom.
  • the second ring heteroatom bonded to the phosphorus atom is preferably also an optionally substituted nitrogen atom.
  • the substituent R ⁇ together with the substituent R ⁇ then particularly preferably forms a bispyrrole group bonded via the pyrrole nitrogen atoms to the phosphorus atom.
  • bispyrrole group corresponds to the definition given at the outset.
  • R ⁇ and R ⁇ together are a 5- to 7-membered heterocycle which is optionally additionally fi-, 2-, 3- or tetra-fused with cycloalkyl, heterocyclo- lauricyl, aryl or hetaryl, wherein the heterocycle and, if present, the fused groups independently of each other one, two, three or four substituents ten, which are selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine, alkoxy, halogen, COOH, carboxylate , SO 3 H, sulfonate, NE 4 E 5 , NE 4 E 5 E 6 X " , nitro, alkoxycarbonyl, acyl and cyano, wherein E 4 , E 5 and E 6 each represent identical or different radicals selected from hydrogen, alkyl, cycloalkyl and aryl
  • the substituent R ⁇ together with the substituent R ß is a divalent group of the formula ## STR5 ## which is bonded via the pyrrole nitrogen atom to the phosphorus atom
  • Py is a pyrrole group
  • I represents a chemical bond or represents O, S, SiR 1 R 2 , NR 3 or optionally substituted C 1 -C 10 -alkylene, preferably CR 4 R 5 ,
  • W is cycloalkyloxy or amino, aryloxy or amino, hetaryloxy or amino
  • R 1 , R 2 , R 3 , R 4 and R 5 independently of one another are hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl,
  • Phosphor chelate compounds in which R ⁇ and R ⁇ together with the phosphorus atom to which they are bonded are preferred for a group of the formulas 11.1 to II.3
  • R 6 and R 7 independently of one another are hydrogen, alkyl, cycloalkyl, aryl, hetaryl, mesylate, tosylate or trifluoromethanesulfonate,
  • R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 and R 27 independently of one another represent hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, W'COOR ', W 1 COO-M + , W (SO 3 ) R *, W' (SO 3 ) -M + , W'PO 3 (R f ) (R 9 ),
  • W ' represents a single bond, a heteroatom, a heteroatom-containing group or a divalent bridging group having 1 to 20 bridging atoms
  • R f , E 13 , E 14 , E 15 are each the same or different radicals selected from hydrogen, alkyl, cycloalkyl or aryl,
  • R g is hydrogen, methyl or ethyl
  • M + is a cation equivalent
  • x is an integer from 1 to 240
  • the radicals R 6 and R 7 are independently selected from hydrogen, C 1 -C 4 -AlkVl, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl , Cs-C ⁇ -cycloalkyl, in particular cyclohexyl and aryl, in particular phenyl.
  • the radicals R 8 , R 9 , R 10 and R 11 are hydrogen.
  • Pnicogen chelate compounds of the formula I in which R ⁇ and R ⁇ together with the phosphorus atom represent a chiral group of the formula II.1 are particularly preferred.
  • the radicals R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen.
  • the further rings are fused aromatic rings.
  • the fused aromatic rings are preferably benzene or naphthalene.
  • Anellissus benzene rings are preferably unsubstituted or have 1, 2 or 3, in particular 1 or 2 substituents, which are preferably selected from alkyl, alkoxy, halogen, SO 3 H, sulfonate, NE 7 E 8 , alkylene NE 7 E 8 , Trifluoromethyl, nitro, carboxyl, alkoxycarbonyl, acyl and cyano.
  • Anellated naphthalenes are preferably unsubstituted or have in the non-fused ring and / or in the fused ring in each case 1, 2 or 3, in particular 1 or 2 of those previously mentioned in the fused benzene rings Substituents on.
  • alkyl is preferably C 1 -C 4 -alkyl and in particular methyl, isopropyl and tert-butyl.
  • Alkoxy is preferably C 1 -C 4 -alkoxy and especially methoxy.
  • Alkoxycarbonyl is preferably C r C 4 alkoxycarbonyl.
  • Halogen is especially fluorine and chlorine.
  • radicals R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 and R 27 are preferably hydrogen.
  • the further rings are preferably fused aromatic rings.
  • the fused aromatic rings are preferably benzene or naphthalene. If desired, these may be substituted as described above for groups II.2.
  • R ⁇ and R ⁇ independently represent substituents which are not linked together.
  • R ⁇ and R ⁇ are then independently of one another selected from aryl and hetaryl radicals which may have 1, 2, 3, 4 or 5 of the abovementioned substituents.
  • R Y or R ⁇ stands or both of these radicals are aryl, which may have one, two or three substituents which are selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and combinations thereof , Preferred radicals R Y and R ⁇ are then, for example, phenyl, o-tolyl, m-xylyl and 3,5-dimethyl-4-methoxyphenyl.
  • the bridging group Y is a chiral group which preferably has at least one chiral center, one chiral axis or chirality plane.
  • the bridging groups Y are preferably selected from groups of formulas III.a and III. b
  • Y preferably represents a group of the formula IIIa, in which R IV and R V independently of one another represent C r C 4 -alkyl or C r C 4 -alkoxy.
  • R N and R v are selected from methyl, ethyl, isopropyl, tert -butyl and methoxy.
  • R 1 , R ", R 111 , R v ⁇ , R v " and R v ⁇ " are hydrogen.
  • Y is lll.a a group of the formula wherein R 1 and R VIII "un ⁇ interdependent for -C 4 alkyl or Ci-C 4 -alkoxy. Particularly preferably, R 1 and R VIII" for tert -butyl.. Particularly preferably, in these compounds, R ", R 1", R IV, R V, R VI, R v "is hydrogen. In addition, preferably, in these compounds, R 1" v ⁇ independently C1 and R 4 -alkyl or C 1 -C 4 -alkoxy. Particularly preferred are R MI and R v ⁇ are independently selected from methyl, ethyl, isopropyl, tert-butyl and methoxy.
  • Y is preferably a group of the formula IIIa, in which R “and R v " are hydrogen.
  • R 1, R “v ⁇ , R lv, R v, R and R VIII" 1 independently represent -C 4 alkyl or C 1 -C 4 -alkoxy.
  • R 1 , R 1 ", R IV , R V , R V ⁇ and R v ⁇ " are independently selected from methyl, ethyl, isopropyl, tert-butyl and methoxy.
  • Y is preferably a group of the formula III. b, wherein R 1 to R x "are hydrogen.
  • Y is preferably a group of the formula III. b, wherein R 1 and R x "unab ⁇ pending for C r C 4 alkyl or C 1 -C 4 -alkoxy are from each other.
  • R 1 and R x ' are independently selected from methyl, ethyl, isopropyl, tert. Butyl, methoxy and alkoxycarbonyl, preferably methoxycarbonyl.
  • the radicals R 11 to R x ⁇ are hydrogen.
  • Another object of the invention is a chiral catalyst comprising emerges ⁇ least a complex with a metal of the VIII. Subgroup of the Periodic Table, the at least one chiral phosphorochelate compound as defined above, as defined above.
  • the chiral catalysts according to the invention and used according to the invention have at least one of the compounds described above as ligands.
  • you can still at least one other ligand which is preferably selected from halides, amines, carboxylates, acetylacetonate, aryl or alkyl sulfonates, hydride, CO, olefins, dienes, cycloolefins, nitriles, N-containing heterocycles , Aromatics and heteroaromatics, ethers, PF 3 , phospholes, phosphabenzenes and mono-, di- and polydentate phosphine, phosphinite, phosphonite, phosphoramidite and phosphite ligands aufwei ⁇ sen.
  • the transition metal is preferably a metal of the I., VI., VII. Or VIII. Subgroup of the Periodic Table of the Elements. More preferably, the transition metal is selected from the metals of Group VIII (i.e., Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, Pt). In particular, the transition metal is iridium, ruthenium, rhodium, palladium or platinum.
  • Another object of the invention is a process for preparing chiral Ver ⁇ compounds by reacting a prochiral compound containing at least one ethylenically unsaturated double bond, with a substrate in the presence of a chiral catalyst, as described above. All that is required is that at least one of the ligands used or the catalytically active species is entirely chiral. In general, certain transition metal complexes are formed as catalytically active species under the reaction conditions of the individual processes for producing chiral compounds.
  • catalytically active species of the general formula H x M y (CO) z L q are formed under hydroformylation conditions from the particular catalysts or catalyst precursors used, where M is a transition metal, L is a phosphorochelate compound and q, x, y , z are integers, depending on the valency and type of metal and the binding of ligand L, stand.
  • z and q are independently of one another at least a value of 1, such. B. 1, 2 or 3.
  • the sum of z and q is preferably from 1 to 5.
  • the complexes may, if desired, additionally have at least one of the further ligands described above.
  • the catalytically active species is preferably present as a homogeneous single-phase solution in a suitable solvent.
  • This solution may additionally contain free ligands.
  • the process according to the invention for the preparation of chiral compounds is preferably a hydrogenation, hydroformylation, hydrocyanation, carbonylation, hydroacylation (intramolecular and intermolecular), hydroamidation, hydroesterification, hydrosilylation, hydroboration, aminolysis (hydroamination), alcoholysis (hydroxylation). Alkoxy addition), isomerization, transfer hydrogenation, metathesis, cyclopropanation, aldol condensation, allylic alkylation, or a [4 + 2] cycloaddition (Diels-Alder reaction).
  • the process according to the invention for preparing chiral compounds is particularly preferably a 1,2-addition, in particular a hydrogenation or a 1-hydro-2-carboo addition.
  • 1-Hydro-2-carbo-addition refers to an addition reaction in which, after the reaction, hydrogen is bonded to one atom of the double bond and a carbon atom-containing group is bonded to the other. Double bond isomerizations during addition are allowed.
  • 1-hydro-2-carbo-addition in unsymmetrical substrates should not be referred to as a preferred addition of the carbon fragment to the C2 atom, since the selectivity with respect to the orientation of the addition of the generally to be added and depends on the catalyst used.
  • “1-hydro-2-carbo-” is in this sense synonymous with "1-carbo-2-hydro-”.
  • reaction conditions of the processes according to the invention for the preparation of chiral compounds, except for the chiral catalyst used, generally correspond to those of the corresponding asymmetric processes.
  • Suitable reactors and reaction conditions can thus be taken from the relevant literature on the respective method and routinely adapted by the person skilled in the art.
  • Suitable temperatures Obstem ⁇ are generally in a range from -100 to 500 0 C, preferably in a range from -80 to 250 0 C.
  • Suitable reaction pressures are generally in a range of 0.0001 to 600 bar, preferably from 0.5 to 300 bar.
  • the processes can generally be carried out continuously, semicontinuously or batchwise.
  • Suitable reactors for the continuous reaction are known in the art and z. As described in Ullmann's Encyclopedia of Industrial Chemistry, Vol.
  • suitable solvents are z.
  • aromatics such as toluene and xylene
  • hydrocarbons or mixtures of hydrocarbons are also suitable.
  • halogenated in particular chlorinated hydrocarbons, such as dichloromethane, chloroform or 1, 2-dichloroethane.
  • Further solvents are esters of aliphatic carboxylic acids with alkanols, for example ethyl acetate or Texanol®, ethers, such as tert-butyl methyl ether, dioxane-1, 4 and tetrahydrofuran, and dimethylformamide.
  • ligands are sufficiently hydrophilized, it is also possible to use alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, ketones, such as acetone and methyl ethyl ketone, etc. Further, as a solvent and so-called “ionic liquids" can be used.
  • liquid salts for example N, N'-dialkylimidazolium salts, such as the N-butyl-N'-methylimidazolium salts, tetraalkylammonium salts, such as the tetra-n-butylammonium salts, N-alkylpyridinium salts, such as the n-butylpyridinium salts, and tetraalkylphosphonium salts, such as Trishexyl (tetradecyl) phosphonium salts, e.g.
  • N, N'-dialkylimidazolium salts such as the N-butyl-N'-methylimidazolium salts
  • tetraalkylammonium salts such as the tetra-n-butylammonium salts
  • N-alkylpyridinium salts such as the n-butylpyridinium salts
  • tetrafluoroborates acetates, tetrachloroaluminates, hexafluorophosphates, chlorides and tosylates.
  • the solvent used may also be a starting material, product or by-product of the particular reaction.
  • Suitable prochiral ethylenically unsaturated compounds for the process according to the invention are in principle all prochiral compounds which contain one or more ethylenically unsaturated carbon-carbon or carbonyl groups.
  • prochiral olefins hydroformylation, intermolecular hydroacylation, hydrocyanation, hydrosilylation, carbonylation, hydroamidation, hydroesterification, aminolysis, alcoholysis, cyclopropanation, hydroboration, Diels-Alder reaction, metathesis
  • Suitable prochiral ethylenically unsaturated olefins are generally compounds of the formula
  • R A and R B and / or R c and R D are radicals of different definitions. It goes without saying that for the production according to the invention of chiral compounds, those reacted with the prochiral ethylenically unsaturated compound Substrates and possibly also the stereoselectivity with respect to the addition of a particular substituent to a particular carbon atom of the CC double bond can be chosen so that at least one chiral carbon atom results.
  • R A, R B, R c and R D in compliance with the above-mentioned condition is independently selected from hydrogen, alkyl, cycloalkyl, heterocyclo alkyl, aryl, hetaryl, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy, hetaryloxy, hydroxy, thiol , Polyalkylene oxide, polyalkyleneimine, COOH, carboxylate, SO 3 H, sulfonate, NE 16 E 17 , NE 16 E 17 E 18 X ' , halogen, nitro, acyl, acyloxy or cyano, wherein E 16 , E 17 and E 18 are each the same or different radicals selected from among hydrogen, alkyl, cycloalkyl, or aryl and X- is an anion equivalent,
  • alkyl radicals have 1, 2, 3, 4, 5 or more substituents selected from cycloalkyl, heterocycloalkyl, aryl, hetaryl, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy, hetaryloxy, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine, COOH, carboxylate, SO 3 H, sulfonate, NE 19 E 20 , NE 19 E 20 E 21 X ' , halogen, nitro, acyl, acyloxy or cyano, wherein E 19 , E 20 and E 21 are each the same or different radicals selected from hydrogen , Alkyl, cycloalkyl, or aryl and X 'is an anion equivalent,
  • cycloalkyl, heterocycloalkyl, aryl and hetaryl radicals R A , R B , R c and R D may each have 1, 2, 3, 4, 5 or more substituents selected from alkyl and those previously described for the Alkyl substituents R A , R B , R c and R D substituents th, or
  • R A , R B , R c and R D together with the CC double bond to which they are attached represent a mono- or polycyclic compound.
  • Suitable prochiral olefins are olefins having at least 4 carbon atoms and terminal or internal double bonds which are straight-chain, branched or cyclic in structure.
  • Suitable ⁇ -olefins are, for. 1-butene, 1-pentene, 1-hexene, 1-heptene, 1-octene, 1-nonene, 1-decene, 1-undecene, 1-dodecene, 1-octadecene, etc.
  • Suitable linear (straight-chain) internal olefins are preferably C 4 -C 2 o-olefins, such as 2-butene, 2-pentene, 2-hexene, 3-hexene, 2-heptene, 3-heptene, 2-octene, 3-octene , 4-octene etc.
  • Suitable branched internal olefins are preferably C 4 -C 2 o-olefins such as 2-methyl butene-2, 2-methyl-2-pentene, 3-methyl-2-pentene, branched, internal heptene mixtures, branched, internal octene mixtures, branched, internal nonene mixtures, branched, internal decene mixtures, branched, internal undecene mixtures, branched, internal dodecene mixtures, etc.
  • C 4 -C 2 o-olefins such as 2-methyl butene-2, 2-methyl-2-pentene, 3-methyl-2-pentene, branched, internal heptene mixtures, branched, internal octene mixtures, branched, internal nonene mixtures, branched, internal decene mixtures, branched, internal undecene mixtures, branched, internal dodecene mixtures, etc.
  • Suitable olefins to be hydroformylated are furthermore C 5 -C 8 -cycloalkenes, such as cyclopentene, cyclohexene, cycloheptene, cyclooctene and their derivatives, such as. B. de ⁇ Ren C 1 -C 20 alkyl derivatives having 1 to 5 alkyl substituents.
  • Suitable olefins to be hydroformylated are furthermore vinylaromatics, such as styrene, ⁇ -methylstyrene, 4-isobutylstyrene, etc., 2-vinyl-6-methoxynaphthalene, (3-ethenylphenyl) phenylketone, (4-ethenylphenyl) -2-thienyl ketone, 4-ethenyl -2-fluorobiphenyl, 4- (1,3-dihydro-1-oxo-2H-isoindol-2-yl) styrene, 2-ethenyl-5-benzoylthiophene, (3-ethenylphenyl) phenyl ether, propenylbenzene, 2-propenylphenol, isobutyl 4-propenylbenzene, phenyl vinyl ethers and cyclic enamides, e.g.
  • 2,3-dihydro-1, 4-oxazines such as 2,3-dihydro-4-tert-butoxycarbonyl-1,4-oxazine.
  • Suitable olefins to be hydroformylated are furthermore ⁇ , ⁇ -ethylenically unsaturated mono- and / or dicarboxylic acids, their esters, monoesters and amides, such as acrylic acid, methacrylic acid, maleic acid, fumaric acid, crotonic acid, itaconic acid, methyl 3-pentenoate,
  • Suitable substrates are also di- or polyenes with isolated or conjugated double bonds. These include z. B. 1, 3-butadiene, 1, 4-pentadiene, 1, 5-hexadiene, 1, 6-heptadiene, 1, 7-octadiene, 1, 8-nonadiene, 1, 9-decadiene, 1, 10-undecadiene, 1, 11-dodecadiene, 1, 12-tridecadiene, 1, 13-tetradecadiene, vinylcyclohexene, dicyclopentadiene, 1, 5,9-cyclooctatriene and Butadienhomo- and copolymers.
  • prochiral ethylenically unsaturated compounds which are important as synthesis building blocks are, for example, P-isobutylstyrene, 2-vinyl-6-methoxynaphthalene, (3-ethenylphenyl) phenylketone, (4-ethenylphenyl) -2-thienyl ketone, 4-ethenyl-2-fluorobiphenyl, 4- (1,3-dihydro-1 -oxo-2H-isoindol-2-yl) styrene, 2-ethenyl-5-benzoylthiophene, (3-ethenylphenyl) phenyl ether, propenylbenzene, 2-propenylphenol, isobutyl-4-propenylbenzene, phenylvinyl ethers and cyclic enamides, e.g.
  • 2,3-dihydro-1, 4-oxazines such as 2,3-dihydro-4-tert-butoxycarbonyl-1, 4-oxazine.
  • the aforementioned olefins can be used individually or in the form of mixtures.
  • the chiral catalysts according to the invention and used according to the invention are prepared in situ in the reactor used for the reaction. If desired, however, the catalysts according to the invention can also be prepared separately and isolated by customary processes.
  • the catalysts of the invention can be z.
  • Suitable activating agents are, for. B. Bronsted acids, Lewis acids, such as. B. BF 3 , AICI 3 , ZnCl 2 , and Lewis bases.
  • Suitable catalyst precursors are very generally transition metals, transition metal compounds and transition metal complexes.
  • Suitable rhodium compounds or complexes are, for. Rhodium (II) and rhodium (III) salts, such as rhodium (III) chloride, rhodium (III) nitrate, rhodium (III) sulfate, potassium rhodium sulfate, rhodium (II) or Rhodium (III) carboxylate, rhodium (II) and rhodium (III) acetate, rhodium (III) oxide, salts of rhodium (III) acid, trisammonium hexachlororhodate (III), etc.
  • Rhodium (II) and rhodium (III) salts such as rhodium (III) chloride, rhodium (III) nitrate, rhodium (III) sulfate, potassium rhodium sulfate, rhodium (II) or Rh
  • rhodium complexes are suitable such as Rh 4 (CO) 12 , rhodiumbiscarbonylacetylacetonate, acetylacetonato-bis-ethyl rhodium (I), etc.
  • ruthenium salts or compounds are, for example, ruthenium (III) chloride, ruthenium (IV), ruthenium (VI) or ruthenium (VIII) oxide, alkali salts of ruthenium oxygen acids such as K 2 RuO 4 or KRuO 4 or complex compounds, such as.
  • RuHCl (CO) (PPh 3 ) 3 ruthenium (III) chloride, ruthenium (IV), ruthenium (VI) or ruthenium (VIII) oxide
  • alkali salts of ruthenium oxygen acids such as K 2 RuO 4 or KRuO 4 or complex compounds, such as.
  • metal carbonyls of ruthenium such as trisruthenium dodecacarbonyl or hexaruthenium octadecacarbonyl, or mixed forms in which CO are partly replaced by ligands of the formula PR 3 , such as Ru (CO) 3 (PPh 3 ) 2 , in the process according to the invention.
  • Suitable iron compounds are for. As iron (III) acetate and iron (III) nitrate and the carbonyl complexes of iron.
  • Suitable nickel compounds are nickel fluoride and nickel sulfate.
  • a suitable for the preparation of a nickel catalyst nickel complex is z. Bis (1,5-cyclooctadiene) nickel (O).
  • the metal concentration in the reaction medium is in a range of about 1 to 10,000 ppm.
  • the molar ratio of monopnicogen ligand to transition metal is generally in the range of about 0.5: 1 to 1000: 1, preferably 1: 1 to 500: 1.
  • catalysts described above can be suitably, for. B. by attachment via suitable as anchor groups functional groups, adsorption, grafting, etc. to a ge suitable carrier, eg. Example of glass, silica gel, resins, polymers, etc., be immobilized. They are then also suitable for use as solid phase catalysts.
  • the process according to the invention is a hydrogenation (1,2-H, H addition). How to get through
  • prochiral compound containing at least one ethylenically unsaturated double bond Reacting a prochiral compound containing at least one ethylenically unsaturated double bond, with hydrogen in the presence of a chiral catalyst, as described above, to corresponding chiral compounds having a single bond.
  • Prochiral olefins lead to chiral carbonaceous compounds, prochiral ketones to chiral alcohols, and prochiral imines to chiral amines.
  • the process according to the invention is a reaction with carbon monoxide and hydrogen, which is referred to below as hydroformylation.
  • the hydroformylation can be carried out in the presence of one of the abovementioned solvents.
  • the molar ratio of mono (pseudo) pnicogen ligand to metal of the VIII. Ne ⁇ ben distr is generally in a range of about 1: 1 to 1000: 1, vorzugswei ⁇ se 2: 1 to 500: 1.
  • hydroformylation catalyst is prepared in situ, at least one ligand which can be used according to the invention, a compound or a complex of a transition metal and optionally an activating agent in an inert solvent under the hydroformylation conditions brings to reaction.
  • the transition metal is preferably a metal of the VIII.
  • Mau ⁇ group of the Periodic Table of the Elements more preferably cobalt, ruthenium, iridium, rhodium and palladium.
  • rhodium is used.
  • composition of the synthesis gas used in the process according to the invention of carbon monoxide and hydrogen can vary within wide ranges.
  • the molar ratio of carbon monoxide and hydrogen is usually about 5:95 to 70:30, preferably about 40:60 to 60:40. Particularly preferred is a molar ratio of carbon monoxide and hydrogen in the range of about 1: 1 is used.
  • the temperature during the hydroformylation reaction is generally in a range from about Be ⁇ 20 to 180 0 C, preferably about 50 to 150 0 C.
  • the pressure is in a range of about 1 to 700 bar, preferably from 1 to 600 bar, in particular 1 to 300 bar.
  • the reaction pressure can be varied depending on the activity of the hydroformylation catalyst of the invention used.
  • the novel catalysts based on phosphorus-containing compounds allow a reaction in a range of low pressures, such as in the range of 1 to 100 bar.
  • hydroformylation catalysts according to the invention and the hydroformylation catalysts according to the invention can be separated off from the starting point of the hydroformylation reaction by customary methods known to the person skilled in the art and can generally be used again for the hydroformylation.
  • the asymmetric hydroformylation according to the process of the invention is characterized by a high stereoselectivity.
  • the catalysts according to the invention and the catalysts used according to the invention also generally have a high regioselectivity.
  • the catalysts generally have a high stability under the hydroformylation conditions, so that with you usually longer catalyst life can be achieved than with the state of Technically known catalysts based on conventional chelating ligands.
  • the catalysts according to the invention and those used according to the invention furthermore exhibit high activity, so that as a rule the corresponding aldehydes or alcohols are obtained in good yields.
  • the catalysts used for the hydrocyanation include complexes of a metal of subgroup VIII, in particular cobalt, nickel, ruthenium, rhodium, palladium, platinum, preferably nickel, palladium and platinum and very particularly preferably nickel.
  • the preparation of the metal complexes can be carried out as described above. The same applies to the in situ preparation of the hydrocyanation catalysts according to the invention. Methods for hydrocyanation are described in J. March, Advanced Organic Chemistry, 4th ed., Pp. 811-812, which is incorporated herein by reference.
  • the 1-hydro-2-carboo addition is a reaction with carbon monoxide and at least one compound having a nucleophilic group, hereinafter referred to as carbonylation.
  • the carbonylation catalysts also include complexes of a metal of subgroup VIII, preferably nickel, cobalt, iron, ruthenium, rhodium and palladium, in particular palladium.
  • a metal of subgroup VIII preferably nickel, cobalt, iron, ruthenium, rhodium and palladium, in particular palladium.
  • the preparation of the metal complexes can be carried out as described above. The same applies to the in situ preparation of the carbonylation catalysts according to the invention.
  • the compounds are having a nucleophilic group selected from water, alcohols, thiols, carboxylic acid esters, primary and secondary amines.
  • a preferred carbonylation reaction is the conversion of olefins with carbon monoxide and water to carboxylic acids (hydrocarboxylation).
  • the carbonylation can be carried out in the presence of activating agents.
  • Suitable activating agents are, for. B. Bronsted acids, Lewis acids, such as. B. BF 3 , AICI 3 , ZnCl 2 , and Lewis bases.
  • hydroacylation Another important 1,2-addition is hydroacylation.
  • asymmetric intramolecular hydroacylation for example, reaction of an unsaturated aldehyde leads to optically active cyclic ketones.
  • Asymmetric intermolecular hydroacylation is achieved by the reaction of a prochiral olefin an acyl halide in the presence of a chiral catalyst as described above to chiral ketones. Suitable processes for the hydroacylation are described in J. March, Advanced Organic Chemistry, 4th ed., P. 811, to which reference is made here.
  • hydroboration Another important 1,2-addition is hydroboration.
  • a prochiral compound which contains at least one ethylenically unsaturated double bond with borane or a borane source in the presence of a chiral catalyst, as described above, to give chiral trialkylboranes which are obtained as primary alcohols (for example with NaOH / H 2 O 2 ) or can be oxidized to carboxylic acids.
  • Suitable processes for hydroboration are described in J. March, Advanced Organic Chemistry, 4th edition, pages 783-789, to which reference is made here.
  • hydrosilylation Another important 1,2-addition is hydrosilylation.
  • a prochiral compound which contains at least one ethylenically unsaturated double bond with a silane in the presence of a chiral catalyst, as described above, chiral silyl-functionalized compounds are obtained.
  • Prochiral olefins result in chiral silyl-functionalized alkanes.
  • Prochiral ketones result in chiral silyl ethers or alcohols.
  • the transition metal is preferably selected from Pt, Pd, Rh, Ru and Ir. It may be advantageous to use combinations or mixtures of one of the aforementioned catalysts with other catalysts.
  • Suitable additional catalysts include platinum in finely divided form (“platinum black”), platinum chloride and platinum complexes such as hexachloroplatinic acid or divinyldisiloxane-platinum complexes, eg. B. Tetramethyldivinyldisiloxan-platinum complexes.
  • Suitable rhodium catalysts are, for example, (RhCl (P (C 6 H 5 ) S ) 3 ) and RhCl 3 . Also suitable are RuCl 3 and IrCl 3 .
  • Suitable catalysts are also Lewis acids such as AICI 3 or TiCl 4 and peroxides.
  • Suitable silanes are, for.
  • Halogenated silanes such as trichlorosilane, methyldichlorosilane, dimethylchlorosilane and trimethylsiloxydichlorosilane; Alkoxysilanes such as trimethoxysilane, triethoxysilane, methyldimethoxysilane, phenyldimethoxysilane, 1, 3,3,5,5,7,7-heptamethyl-i, 1-dimethoxytetrasiloxane and acyloxysilanes.
  • the reaction temperature in the silylation is preferably in a range of 0 to 140 0 C, more preferably 40 to 120 0 C.
  • the reaction is usually carried out under atmospheric pressure, but can also at elevated pressures, such as. B. Be ⁇ range of about 1, 5 to 20 bar, or reduced pressures such. B. 200 to 600 mbar done.
  • the reaction can be carried out without solvent or in the presence of a suitable solvent.
  • Preferred solvents are, for example, toluene, tetrahydrofuran and chloroform.
  • Another important 1,2-addition is aminolysis (hydroamination).
  • a prochiral compound containing at least one ethylenically unsaturated double bond with ammonia, a primary or a secondary amine in the presence of a chiral catalyst, as described above, to chiral primary, secondary or tertiary amines.
  • Suitable processes for hydroamination are described in J. March, Advanced Organic Chemistry, 4th edition, pages 768-770, to which reference is hereby made.
  • alcoholysis hydro-alkoxy-addition
  • a prochiral compound which contains at least one ethylenically unsaturated double bond
  • alcohols in the presence of a chiral catalyst, as described above, to give chiral ethers.
  • Suitable methods for alcoholysis are described in J. March, Advanced Organic Chemistry, 4th ed., Pp. 763-764, to which reference is made here.
  • Another important reaction is cyclopropanation.
  • a prochiral compound containing at least one ethylenically unsaturated double bond is reacted with a diazo compound in the presence of a chiral catalyst as described above to give chiral cyclopropanes.
  • Another important reaction is metathesis.
  • a prochiral compound containing at least one ethylenically unsaturated double bond with another olefin in the presence of a chiral catalyst, as described above leads to chiral hydrocarbons.
  • allylic alkylation Another important reaction is allylic alkylation.
  • a prochiral ketone or aldehyde with an allylic alkylating agent in the presence of a chiral catalyst, as described above, chiral hydrocarbons are obtained.
  • Another object of the invention is the use of catalysts comprising at least one complex of a metal of VIII.
  • optically active compounds which can be prepared by the process according to the invention are substituted and unsubstituted alcohols or phenols, amines, amides, esters, carboxylic acids or anhydrides, ketones, olefins, aldehydes, nitriles and hydrocarbons.
  • Optically active aldehydes prepared by the asymmetric hydroformylation process according to the invention include, for example, S-2- (p-isobutylphenyl) propionaldehyde, S-2- (6-methoxynaphthyl) propionaldehyde, S-2- (3-benzoylphenyl) propionaldehyde, S-2 - (p-thienoylphenyl) propionaldehyde, S-2- (3-fluoro-4-phenyl) phenylpropionaldehyde, S-2- [4- (1,3-dihydro-1-oxo-2H-isoindol-2-yl) -phenyl propionaldehyde, S-2- (2-methylacetaldehyde) -5-benzoylthiophene, etc.
  • Other optically active compounds which can be prepared by the process according to the invention are described in Kirk-Othmer, Encyclopedia of
  • the inventive method allows the production of optically active products with high enantioselectivity and, if necessary, regioselectivity, for. B. in the hydroformylation. Enantiomeric excesses (ee) of at least 50%, preferably at least 60% and in particular at least 70% can be achieved.
  • the isolation of the products obtained succeeds according to customary processes known to the person skilled in the art. These include, for example, solvent extraction, crystallization, distillation, evaporation z. In a wiper blade or falling film evaporator, etc.
  • optically active compounds obtained by the process according to the invention may be subjected to one or more secondary reactions.
  • Such methods are known to the person skilled in the art. These include, for example, the esterification of alcohols, the oxidation of alcohols to aldehydes, N-alkylation of amides, addition of aldehydes to amides, nitrile reduction, acylation of ketones with esters, acylation of amines, etc.
  • asymmetri ⁇ hydroformylation obtained optically active aldehydes of an oxidation to carboxylic acids, reduction to alcohols, aldol condensation to ⁇ , ß-unsaturated Verbindun ⁇ gene, reductive amination to amines, amination to imines, etc., were ⁇ subjected.
  • a preferred derivatization comprises the oxidation of an aldehyde prepared according to the asymmetric hydroformylation process according to the invention to give the corresponding optically active carboxylic acid.
  • a variety of pharmaceutically important compounds such as S-ibuprofen, S-naproxen, S-ketoprofen, S-suprofen, S-fluorobiprofen, S-indoprofen, S-tiaprofenoic acid, etc. can be prepared.
  • Rh (CO) 2 acac and 200 mg of BINASKAT are dissolved in 15.7 g of toluene in an autoclave and stirred with synthesis gas at 9 bar reaction pressure for 4 h at 50 ° C. After addition of 1.75 g of styrene is stirred for 24 h at 50 0 C and 9 bar synthesis gas. The turnover is 93%. The gas chromatographically determined ee value is 66%.

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Abstract

The invention relates to chiral phosphorus chelate compounds, to catalysts comprising such a compound as the ligand, and to asymmetric synthesis methods in the presence of such a catalyst.

Description

Liganden zur asymmetrischen Hydroformylierung Ligands for asymmetric hydroformylation
Beschreibungdescription
Die vorliegende Erfindung betrifft chirale Phosphorchelatverbindungen, Katalysatoren, die eine solche Verbindung als Liganden enthalten sowie Verfahren zur asymmetri¬ schen Synthese in Gegenwart eines solchen Katalysators.The present invention relates to chiral phosphorochelate compounds, catalysts containing such a compound as ligands and to asymmetric synthesis in the presence of such a catalyst.
Asymmetrische Synthese ist die Bezeichnung für Reaktionen, bei denen aus einer pro- chiralen eine chirale Gruppierung erzeugt wird, so dass die stereoisomeren Produkte (Enantiomere oder Diastereomere) in ungleichen Mengen entstehen. Die asymmetri¬ sche Synthese hat vor allem im Bereich der pharmazeutischen Industrie immense Be¬ deutung gewonnen, da häufig nur ein bestimmtes optisch aktives Isomer therapeutisch aktiv ist. Es besteht somit ein ständiger Bedarf an neuen asymmetrischen Syntheseverfahren und speziell Katalysatoren mit einer großen asymmetrischen Induktion für bestimmte Stereozentren, d. h. die Synthese soll zu dem gewünschten Isomeren in hoher optischer Reinheit und in hoher chemischer Ausbeute führen.Asymmetric synthesis is the term for reactions in which a chiral moiety is generated from a chiral moiety, resulting in unequal amounts of stereoisomeric products (enantiomers or diastereomers). The asymmetric synthesis has gained immense importance, above all in the pharmaceutical industry, since frequently only a certain optically active isomer is therapeutically active. Thus, there is a continuing need for new asymmetric synthesis methods, and especially catalysts with a large asymmetric induction for certain stereocenters, i. H. the synthesis should lead to the desired isomer in high optical purity and in high chemical yield.
Eine wichtige Klasse von Reaktionen ist die Addition an Kohlenstoff-Kohlenstoff- und an Kohlenstoff-Heteroatom-Mehrfachbindungen. Dabei wird die Addition an die beiden benachbarten Atome einer C=X-Doppelbindung (X = C, Heteroatom) auch als 1 ,2-Addition bezeichnet. Zusätzlich können Additionsreaktionen nach der Art der ange¬ lagerten Gruppen charakterisiert werden, wobei mit Hydro-Addition die Anlagerung eines Wasserstoffatoms und mit Carbo-Addition die Anlagerung eines kohlenstoffhalti- gen Fragments bezeichnet wird. So bezeichnet eine 1 -Hydro-2-Carbo-Addition eine Anlagerung von Wasserstoff und einer kohlenstoffatomhaltigen Gruppe. Wichtige Ver¬ treter dieser Reaktion sind z. B. die Hydroformylierung, Hydrocyanierung und die Car- bonylierung. Eine weitere sehr bedeutsame Addition an Kohlenstoff-Kohlenstoff- und an Kohlenstoff-Heteroatom-Mehrfachbindungen ist die Hydrierung. Es besteht ein Be- darf an Katalysatoren für asymmetrische Additionsreaktionen an prochirale ethylenisch ungesättigte Verbindungen mit guter katalytischer Aktivität und hoher Stereoselektivi¬ tät.An important class of reactions is the addition of carbon-carbon and carbon-heteroatom multiple bonds. The addition to the two adjacent atoms of a C = X double bond (X = C, heteroatom) is also referred to as 1, 2 addition. In addition, addition reactions can be characterized according to the nature of the attached groups, wherein the addition of a hydrogen atom is designated by hydro addition and the addition of a carbon-containing fragment by carbo-addition. Thus, a 1 -hydro-2-carbo-addition refers to an addition of hydrogen and a carbon atom-containing group. Important representatives of this reaction are e.g. For example, the hydroformylation, hydrocyanation and carbonylation. Another very important addition to carbon-carbon and carbon-heteroatom multiple bonds is hydrogenation. There is a need for catalysts for asymmetric addition reactions to prochiral ethylenically unsaturated compounds with good catalytic activity and high stereoselectivity.
Die Hydroformylierung oder Oxo-Synthese ist ein wichtiges großtechnisches Verfahren und dient der Herstellung von Aldehyden aus Olefinen, Kohlenmonoxid und Wasser¬ stoff. Diese Aldehyde können gegebenenfalls im gleichen Arbeitsgang mit Wasserstoff zu den entsprechenden Oxo-Alkoholen hydriert werden. Die asymmetrische Hydrofor¬ mylierung ist eine wichtige Methode zur Synthese chiraler Aldehyde und ist als Zugang zu chiralen Bausteinen für die Herstellung von Aromastoffen, Kosmetika, Pflanzen- Schutzmitteln und Pharmazeutika von Interesse. Die Hydroformylierungsreaktion selbst ist stark exotherm und läuft im Allgemeinen unter erhöhtem Druck und bei erhöhten Temperaturen in Gegenwart von Katalysatoren ab. Als Katalysatoren werden Co-, Rh-, Ir-, Ru-, Pd- oder Pt-Verbindungen bzw. -komplexe eingesetzt, die zur Aktivitäts- und/oder Selektivitätsbeeinflussung mit N-, P-, As- oder Sb-haltigen Liganden modifi- ziert sein können. Bei der Hydroformylierungsreaktion von Olefinen mit mehr als zwei C-Atomen kann es auf Grund der möglichen CO-Anlagerung an jedes der beiden C-Atome einer Doppelbindung zur Bildung von Gemischen isomerer Aldehyde kom¬ men. Zusätzlich kann es beim Einsatz von Olefinen mit mindestens vier Kohlenstoff¬ atomen durch eine Doppelbindungsisomerisierung zur Bildung von Gemischen isome- rer Olefine und gegebenenfalls auch isomerer Aldehyde kommen. Beim Einsatz chira- ler Katalysatoren kann es zur Bildung von Gemischen enantiomerer Aldehyde kom¬ men. Für eine effiziente asymmetrische Hydroformylierung müssen daher folgende Bedingungen erfüllt sein: 1. hohe Aktivität des Katalysators, 2. hohe Selektivität bezüg¬ lich des gewünschten Aldehyds und 3. hohe Stereoselektivität zugunsten des ge- wünschten Isomers.Hydroformylation or oxo synthesis is an important industrial process and serves to prepare aldehydes from olefins, carbon monoxide and hydrogen. These aldehydes may optionally be hydrogenated in the same operation with hydrogen to the corresponding oxo alcohols. The asymmetric hydroformylation is an important method for the synthesis of chiral aldehydes and is of interest as access to chiral building blocks for the preparation of flavorings, cosmetics, plant protection agents and pharmaceuticals. The hydroformylation reaction itself is highly exothermic and generally runs under elevated pressure and at elevated temperatures in the presence of catalysts. The catalysts used are Co, Rh, Ir, Ru, Pd or Pt compounds or complexes which modify the activity and / or selectivity of N, P, As or Sb-containing ligands - can be decorated. In the hydroformylation reaction of olefins having more than two carbon atoms, it may come to the formation of mixtures of isomeric aldehydes due to the possible CO addition to each of the two carbon atoms of a double bond. In addition, the use of olefins having at least four carbon atoms by double bond isomerization may lead to the formation of mixtures of isomeric olefins and optionally also of isomeric aldehydes. The use of chiral catalysts may lead to the formation of mixtures of enantiomeric aldehydes. For efficient asymmetric hydroformylation, therefore, the following conditions must be met: 1. high activity of the catalyst, 2. high selectivity with respect to the desired aldehyde, and 3. high stereoselectivity in favor of the desired isomer.
Es ist bekannt, bei der Rhodium-Niederdruck-Hydroformylierung phosphorhaltige Li¬ ganden zur Stabilisierung und/oder Aktivierung des Katalysatormetalls einzusetzen. Geeignete phosphorhaltige Liganden sind z. B. Phosphine, Phosphinite, Phosphonite, Phosphite, Phosphoramidite, Phosphole und Phosphabenzole. Die derzeit am weites¬ ten verbreiteten Liganden sind Triarylphosphine, wie z. B. Triphenylphosphin und sul- foniertes Triphenylphosphin, da diese unter den Reaktionsbedingungen eine hinrei¬ chende Stabilität besitzen.It is known to use phosphorus-containing ligands in the rhodium-low-pressure hydroformylation for stabilizing and / or activating the catalyst metal. Suitable phosphorus ligands are z. For example, phosphines, phosphinites, phosphonites, phosphites, phosphoramidites, phospholes and phosphabenzenes. The currently most widely used ligands are triarylphosphines, such as. For example, triphenylphosphine and sulfonated triphenylphosphine, since they have sufficient stability under the reaction conditions.
Die WO 00/56451 beschreibt Hydroformylierungskatalysatoren auf Basis von Phos- phinamiditliganden, worin das Phosphoratom gemeinsam mit einem Sauerstoff atom, an das es gebunden ist, für einen 5- bis 8-gliedrigen Heterocyclus steht.WO 00/56451 describes hydroformylation catalysts based on phosphinamidite ligands, in which the phosphorus atom, together with an oxygen atom to which it is bonded, represents a 5- to 8-membered heterocycle.
Die WO 02/083695 beschreibt Pnicogenchelatverbindungen, bei denen an jedes der Pnicogenatome wenigstens eine Pyrrolgruppe über das pyrrolische Stickstoffatom ge¬ bunden ist. Diese Pnicogenchelatverbindungen eignen sich als Liganden für Hydrofor- mylierungskatalysatoren.WO 02/083695 describes pnicogen chelate compounds in which at least one pyrrole group is bonded to each of the pnicogen atoms via the pyrrole nitrogen atom. These pnicogen chelate compounds are useful as ligands for hydroformylation catalysts.
Die WO 03/018192 beschreibt u. a. Pyrrolphosphorverbindungen, bei denen wenigs- tens eine substituierte und/oder in ein anelliertes Ringsystem integrierte Pyrrolgruppe über ihr pyrrolisches Stickstoffatom kovalent mit dem Phosphoratom verknüpft ist, die sich bei einem Einsatz als Liganden in Hydroformylierungskatalysatoren durch eine sehr gute Stabilität auszeichnen. Die DE-A-103 42 760 beschreibt Pnicogenverbindungen, die zwei Pnicogenatome aufweisen, wobei an beide Pnicogenatome Pyrrolgruppen über ein pyrrolisches Stick¬ stoffatom gebunden sein können und wobei beide Pnicogenatome über eine Methy¬ lengruppe an eine verbrückende Gruppe gebunden sind. Diese Pnicogenverbindungen eignen sich als Liganden für Hydroformylierungskatalysatoren.WO 03/018192 describes, inter alia, pyrrole phosphorus compounds in which at least one substituted and / or pyrrole group integrated into a fused ring system is covalently linked via its pyrrolic nitrogen atom to the phosphorus atom, which has very good stability when used as ligands in hydroformylation catalysts distinguished. DE-A-103 42 760 describes pnicogen compounds which have two pnicogen atoms, pyrrole groups being able to be bound to both pnicogen atoms via a pyrrolic nitrogen atom and both pnicogen atoms being bound to a bridging group via a methylene group. These pnicogen compounds are useful as ligands for hydroformylation catalysts.
Chirale Katalysatoren sind in den zuvor genannten Dokumenten nicht beschrieben.Chiral catalysts are not described in the aforementioned documents.
Es ist bekannt, dass der Einsatz von Chelatliganden, die zwei zur Koordination befä- higte Gruppen aufweisen, sich vorteilhaft auf die erzielte Stereoselektivität in asymmet¬ rischen Hydroformylierungsreaktionen auswirkt. So beschreiben beispielsweise M. M. H. Lambers-Verstappen und J. de Vries in Adv. Synth. Catal. 2003, 345, Nr. 4, S. 478 - 482 die Rhodium-katalysierte Hydroformylierung von ungesättigten Nitrilen, wobei nur mit asymmetrischen BINAPHOS-Liganden eine befriedigende asymmetrische Hydro- formylierung möglich war.It is known that the use of chelating ligands having two groups capable of coordination has an advantageous effect on the achieved stereoselectivity in asymmetric hydroformylation reactions. For example, M.M.H. Lambers-Verstappen and J. de Vries in Adv. Synth. Catal. 2003, 345, No. 4, pp. 478-482, the rhodium-catalyzed hydroformylation of unsaturated nitriles, wherein only with asymmetric BINAPHOS ligands a satisfactory asymmetric hydroformylation was possible.
Die EP-A-O 503 884 beschreibt eine optisch aktive in der 2-Position substituierte 2'-Diphenylphosphin-1 ,1 '-binaphthyl-Verbindung, Katalysatoren auf Basis von Über¬ gangsmetallkomplexen, die eine solche Verbindung als Liganden aufweisen sowie ein Verfahren zur enantioselektiven Silylierung unter Einsatz eines solchen Katalysators.EP-AO 503 884 describes an optically active 2'-substituted 2'-diphenylphosphine-1, 1 '-binaphthyl compound, catalysts based on Über¬ transition metal complexes having such a compound as ligands and a method for enantioselective Silylation using such a catalyst.
Die EP-A-O 614 870 beschreibt ein Verfahren zur Herstellung optisch aktiver Aldehyde durch Hydroformylierung prochiraler 1 -Olefine in Gegenwart eines Rhodiumkomplexes als Hydroformylierungskatalysator, der einen unsymmetrischen phosphoratomhaltigen Liganden mit 1 ,1 '-Binaphthylen-Rückgrat aufweist. Die Herstellung der unsymmetri¬ schen phosphoratomhaltigen Liganden ist mit hohem Syntheseaufwand verbunden. Die EP-A-O 614 901 , EP-A-O 614 902, EP-A-O 614 903, EP-A-O 684 249 und DE-A-198 53 748 beschreiben unsymmetrische phosphoratomhaltige Liganden mit vergleichbarer Struktur.EP-A-0 614 870 describes a process for the preparation of optically active aldehydes by hydroformylation of prochiral 1-olefins in the presence of a rhodium complex as hydroformylation catalyst which has an asymmetrical phosphorus-containing ligand with 1, 1 ' -binaphthylene backbone. The preparation of the unbalanced phosphorus atom-containing ligands is associated with high synthetic effort. EP-A-0 614 901, EP-A-0 614 902, EP-A-0 614 903, EP-A-0 684 249 and DE-A-198 53 748 describe unbalanced phosphorus atom-containing ligands of comparable structure.
Die WO 93/03839 (EP-B-O 600 020) beschreibt einen optisch aktiven Metall-Ligand- Komplex-Katalysator, umfassend eine optisch aktive Pnicogenverbindung als Ligand sowie Verfahren zur asymmetrischen Synthese in Gegenwart eines solchen Katalysa¬ tors.WO 93/03839 (EP-B-0 600 020) describes an optically active metal-ligand complex catalyst comprising an optically active pnicogen compound as ligand and processes for asymmetric synthesis in the presence of such a catalyst.
Die unveröffentlichte deutsche Patentanmeldung P 103 55 066.6 betrifft ein Verfahren zur asymmetrischen Synthese in Gegenwart eines chiralen Katalysators, umfassend wenigstens einen Komplex eines Metalls der VIII. Nebengruppe mit zur Dimerisierung über nicht kovalente Bindungen befähigten Liganden, solche Katalysatoren sowie de- ren Verwendung. Der vorliegenden Erfindung liegt die Aufgabe zu Grunde, chirale Verbindungen und darauf basierende Katalysatoren zur Verfügung zu stellen, die sich zur Herstellung chiraler Verbindungen mit hoher Stereoselektivität und hoher Reaktivität eignen. Diese Katalysatoren sollen sich insbesondere zur Hydroformylierung von Olefinen mit guter Stereoselektivität und hoher Reaktivität eignen.The unpublished German patent application P 103 55 066.6 relates to a process for asymmetric synthesis in the presence of a chiral catalyst, comprising at least one complex of a metal of VIII. Subgroup with ligands capable of dimerization via non-covalent bonds, such catalysts and their use. The object of the present invention is to provide chiral compounds and catalysts based thereon which are suitable for the preparation of chiral compounds with high stereoselectivity and high reactivity. These catalysts should be particularly suitable for the hydroformylation of olefins with good stereoselectivity and high reactivity.
Dementsprechend wurden Phosphorchelatverbindungen der allgemeinen Formel IAccordingly, phosphorus chelate compounds of general formula I
(I)(I)
Rß RYRY RY
gefunden, worinfound in which
Ra und Rß unabhängig voneinander für 5- bis 7-gliedrige heterocyclische Gruppen ste- hen, die über ein Ringstickstoffatom an das Phosphoratom gebunden sind oderR a and R 8 independently of one another represent 5- to 7-membered heterocyclic groups which are bonded to the phosphorus atom via a ring nitrogen atom or
Rα und Rß gemeinsam mit dem Phosphoratom, an das sie gebunden sind, für ei¬ nen 5- bis 7-gliedrigen Heterocyclus stehen, der zusätzlich ein gegebenenfalls substituiertes Stickstoffatom und ein weiteres unter Sauerstoff und gegebenen¬ falls substituiertem Stickstoff ausgewähltes Heteroatom aufweist, die beide direkt an das Phosphoratom gebunden sind,R α and R β, together with the phosphorus atom to which they are attached, stand for a 5- to 7-membered heterocycle which additionally has an optionally substituted nitrogen atom and a further heteroatom selected from oxygen and optionally substituted nitrogen, both bound directly to the phosphorus atom,
RY und Rδ unabhängig voneinander für Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl oder Hetaryl stehen, wobei die Alkylreste 1 , 2, 3, 4 oder 5 Substituenten, ausgewählt unter Cycloalkyl, Heterocycloalkyl, Aryl, Hetaryl, Alkoxy, Cycloalkoxy, Heterocyc- loalkoxy, Aryloxy, Hetaryloxy, Hydroxy, Thiol, Polyalkylenoxid, Polyalkylenimin,R Y and R δ independently of one another are alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where the alkyl radicals have 1, 2, 3, 4 or 5 substituents selected from cycloalkyl, heterocycloalkyl, aryl, hetaryl, alkoxy, cycloalkoxy, heterocycloalkoxy , Aryloxy, hetaryloxy, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine,
COOH, Carboxylat, SO3H, Sulfonat, NE1E2, NE1 E2E3X-, Halogen, Nitro, Acyl oder Cyano aufweisen können, worin E1, E2 und E3 jeweils gleiche oder verschiedene Reste, ausgewählt unter Wasserstoff, Alkyl, Cycloalkyl, oder Aryl bedeuten und X' für ein Anionäquivalent steht,COOH, carboxylate, SO 3 H, sulfonate, NE 1 E 2 , NE 1 E 2 E 3 X-, halogen, nitro, acyl or cyano, wherein E 1 , E 2 and E 3 are each the same or different radicals selected under hydrogen, alkyl, cycloalkyl, or aryl and X 'is an anion equivalent,
und wobei die Cycloalkyl-, Heterocycloalkyl-, Aryl- und Hetarylreste Rv und Rδ 1 , 2, 3, 4 oder 5 Substituenten aufweisen können, die ausgewählt sind unter Alkyl und den zuvor für die Alkylreste RY und Rδ genannten Substituenten, oderand wherein the cycloalkyl, heterocycloalkyl, aryl and hetaryl radicals R v and R δ may have 1, 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents previously mentioned for the alkyl radicals R Y and R δ , or
X für O, S, SiRεRξ oder NRη steht, worin Rε, Rξ und Rη unabhängig voneinander für Wasserstoff, Alkyl, Cycioalkyl, Heterocycloalkyl, Aryl oder Hetaryl stehen, und Y für eine chirale zweiwertige verbrückende Gruppe steht.X ξ is O, S, SiR ε R or NR η, where R ε, R ξ and η R is independently hydrogen, are alkyl, Cycioalkyl, heterocycloalkyl aryl or hetaryl, and Y stands for a chiral divalent bridging group.
"Chirale Verbindungen" sind im Rahmen der vorliegenden Erfindung Verbindungen mit wenigstens einem Chiralitätszentrum (d. h. wenigstens einem asymmetrischen Atom, insbesondere wenigstens einem asymmetrischen C-Atom oder P-Atom), mit Chirali- tätsachse, Chiralitätsebene oder Schraubenwindung."Chiral compounds" in the context of the present invention are compounds having at least one chiral center (that is to say at least one asymmetric atom, in particular at least one asymmetric C atom or P atom), with chirality axis, chirality plane or helical turn.
Der Begriff "chiraler Katalysator" wird im Rahmen der vorliegenden Erfindung weit ver¬ standen. Er umfasst sowohl Katalysatoren, die wenigstens einen chiralen Liganden aufweisen, als auch Katalysatoren mit an sich achiralen Liganden, die auf Grund der Anordnung der Liganden infolge nichtkovalenter Wechselwirkungen und/oder der An¬ ordnung der Liganden in komplex gebundener Form Zentrumschiralität, axiale Chirali- tät, planare Chiralität oder Helicität aufweisen.The term "chiral catalyst" is widely understood in the context of the present invention. It comprises both catalysts which have at least one chiral ligand and also catalysts with intrinsically achiral ligands which, owing to the arrangement of the ligands as a result of noncovalent interactions and / or the arrangement of the ligands in complexed form, have center chirality, axial chirality , planar chirality or helicity.
"Achirale Verbindungen" sind Verbindungen, die nicht chiral sind."Achiral connections" are compounds that are not chiral.
Unter einer "prochiralen Verbindung" wird eine Verbindung mit wenigstens einem pro- chiralen Zentrum verstanden. "Asymmetrische Synthese" bezeichnet eine Reaktion, bei der aus einer Verbindung mit wenigstens einem prochiralen Zentrum eine Verbin- düng mit wenigstens einem Chiralitätszentrum, einer Chiralitätsachse, Chiralitätsebene oder Schraubenwindung erzeugt wird, wobei die stereoisomeren Produkte in unglei¬ chen Mengen entstehen.A "prochiral compound" is understood to mean a compound having at least one prochiral center. "Asymmetric synthesis" refers to a reaction in which a compound having at least one prochiral center is formed from a compound having at least one center of chirality, a chirality axis, a plane of chirality, or a helical coil, whereby the stereoisomeric products are formed in uneven amounts.
"Stereoisomere" sind Verbindungen gleicher Konstitution aber unterschiedlicher Atom- anordnung im dreidimensionalen Raum."Stereoisomers" are compounds of the same constitution but with different atomic arrangements in three-dimensional space.
"Enantiomere" sind Stereoisomere, die sich zueinander wie Bild zu Spiegelbild verhal¬ ten. Der bei einer asymmetrischen Synthese erzielte Εnantiomeren-Überschuss" (enantiomeric excess, ee) ergibt sich dabei nach folgender Formel: ee[%] = (R-S)/(R+S) x 100. R und S sind die Deskriptoren des CIP-Systems für die beiden"Enantiomers" are stereoisomers which behave in mirror-image relationship to one another. The "enantiomeric excess" obtained in an asymmetric synthesis (enantiomeric excess, ee) is given by the following formula: ee [%] = (RS) / ( R + S) x 100. R and S are the descriptors of the CIP system for the two
Enantiomeren und geben die absolute Konfiguration am asymmetrischen Atom wieder. Die enantiomerenreine Verbindung (ee = 100 %) wird auch als "homochirale Verbin¬ dung" bezeichnet.Enantiomers and represent the absolute configuration of the asymmetric atom. The enantiomerically pure compound (ee = 100%) is also referred to as "homochiral compound".
Das erfindungsgemäße Verfahren führt zu Produkten, die bezüglich eines bestimmten Stereoisomers angereichert sind. Der erzielte "Enantiomeren-Überschuss" (ee) beträgt in der Regel wenigstens 20 %, bevorzugt wenigstens 50 %, insbesondere wenigstens 80 %.The process of the invention results in products that are enriched in a particular stereoisomer. The achieved "enantiomeric excess" (ee) is generally at least 20%, preferably at least 50%, in particular at least 80%.
"Diastereomere" sind Stereoisomere, die nicht enantiomer zueinander sind. Im Folgenden umfasst der Ausdruck "Alkyl" geradkettige und verzweigte Alkylgruppen. Vorzugsweise handelt es sich dabei um geradkettige oder verzweigte C1-C20-AIkVl, bevorzugterweise CrCi2-AIkVl-, besonders bevorzugt C1-C8-AIkVl- und ganz besonders bevorzugt CrC4-Alkylgruppen. Beispiele für Alkylgruppen sind insbesondere Methyl, Ethyl, Propyl, Isopropyl, n-Butyl, 2-Butyl, sec.-Butyl, tert.-Butyl, n-Pentyl, 2-Pentyl, 2-Methylbutyl, 3-Methylbutyl, 1 ,2-Dimethylpropyl, 1 ,1-Dimethylpropyl, 2,2-Dimethylpropyl, 1 -Ethylpropyl, n-Hexyl, 2-Hexyl, 2-Methylpentyl, 3-Methylpentyl, 4-Methylpentyl, 1 ,2-Dimethylbutyl, 1 ,3-Dimethylbutyl, 2,3-Dimethylbutyl, 1 ,1-Dimethylbutyl, 2,2-Dimethylbutyl, 3,3-Dimethylbutyl, 1 ,1 ,2-Trimethylpropyl,"Diastereomers" are stereoisomers that are not enantiomeric to one another. In the following, the term "alkyl" includes straight-chain and branched alkyl groups. Preferably, it is straight-chain or branched C 1 -C 20 -alkyl, preferably CrCl 2 -AIkVl-, particularly preferably C 1 -C 8 -AIkVl- and most preferably C r C 4 alkyl groups. Examples of alkyl groups are in particular methyl, ethyl, propyl, isopropyl, n-butyl, 2-butyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methylbutyl, 3-methylbutyl, 1, 2 -Dimethylpropyl, 1, 1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 2-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl , 2,3-dimethylbutyl, 1, 1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1, 1, 2-trimethylpropyl,
1 ,2,2-Trimethylpropyl, 1 -Ethylbutyl, 2-Ethylbutyl, 1 -Ethyl- 2-methylpropyl, n-Heptyl, 2-Heptyl, 3-Heptyl, 2-Ethylpentyl, 1 -Propylbutyl, n-Octyl, 2-Ethylhexyl, 2-Propylheptyl, Nonyl, Decyl.1, 2,2-trimethylpropyl, 1-ethylbutyl, 2-ethylbutyl, 1-ethyl-2-methylpropyl, n-heptyl, 2-heptyl, 3-heptyl, 2-ethylpentyl, 1-propylbutyl, n-octyl, 2- Ethylhexyl, 2-propylheptyl, nonyl, decyl.
Der Ausdruck "Alkyl" umfasst auch substituierte Alkylgruppen, welche im Allgemeinen 1 , 2, 3, 4 oder 5, bevorzugt 1 , 2 oder 3 und besonders bevorzugt 1 Substituenten, aus¬ gewählt aus den Gruppen Cycloalkyl, Aryl, Hetaryl, Halogen, NE1E2, NE1E2E3+, COOH, Carboxylat, -SO3H und Sulfonat, tragen können.The term "alkyl" also includes substituted alkyl groups which are generally 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent aus¬ selected from the groups cycloalkyl, aryl, hetaryl, halogen, NE 1 E 2 , NE 1 E 2 E 3+ , COOH, carboxylate, -SO 3 H and sulfonate.
Der Ausdruck "Alkylen" im Sinne der vorliegenden Erfindung steht für geradkettige oder verzweigte Alkandiyl-Gruppen mit 1 bis 4 Kohlenstoffatomen.The term "alkylene" in the context of the present invention stands for straight-chain or branched alkanediyl groups having 1 to 4 carbon atoms.
Der Ausdruck "Cycloalkyl" umfasst im Sinne der vorliegenden Erfindung unsubstituierte als auch substituierte Cycloalkylgruppen, vorzugsweise C5-C7-Cycloalkylgruppen, wie Cyclopentyl, Cyclohexyl oder Cycloheptyl, die im Falle einer Substitution, im Allgemei¬ nen 1 , 2, 3, 4 oder 5, bevorzugt 1 , 2 oder 3 und besonders bevorzugt 1 Substituenten, ausgewählt aus den Gruppen Alkyl, Alkoxy und Halogen, tragen können.The term "cycloalkyl" in the context of the present invention comprises unsubstituted as well as substituted cycloalkyl groups, preferably C 5 -C 7 -cycloalkyl groups, such as cyclopentyl, cyclohexyl or cycloheptyl, which in the case of a substitution, in general 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent selected from the groups alkyl, alkoxy and halogen, can carry.
Der Ausdruck "Heterocycloalkyl" im Sinne der vorliegenden Erfindung umfasst gesät- tigte, cycloaliphatische Gruppen mit im Allgemeinen 4 bis 7, vorzugsweise 5 oder 6 Ringatomen, in denen 1 oder 2 der Ringkohlenstoffatome durch Heteroatome, vor¬ zugsweise ausgewählt aus den Elementen Sauerstoff, Stickstoff und Schwefel, ersetzt sind und die gegebenenfalls substituiert sein können, wobei im Falle einer Substitution, diese heterocycloaliphatischen Gruppen 1 , 2 oder 3, vorzugsweise 1 oder 2, besonders bevorzugt 1 Substituenten, ausgewählt aus Alkyl, Aryl, COORf, COO"M+ und NE1E2, bevorzugt Alkyl, tragen können. Beispielhaft für solche heterocycloaliphatischen Grup¬ pen seien Pyrrolidinyl, Piperidinyl, 2,2,6,6-Tetramethylpiperidinyl, Imidazolidinyl, Pyra- zolidinyl, Oxazolidinyl, Morpholidinyl, Thiazolidinyl, Isothiazolidinyl, Isoxazolidinyl, Pipe- razinyl-, Tetrahydrothiophenyl, Tetrahydrofuranyl, Tetrahydropyranyl, Dioxanyl ge- nannt. Der Ausdruck "Aryl" umfasst im Sinne der vorliegenden Erfindung unsubstituierte als auch substituierte Arylgruppen, und steht vorzugsweise für Phenyl, ToIyI, XyIyI, Mesityl, Naphthyl, Fluorenyl, Anthracenyl, Phenanthrenyl oder Naphthacenyl, besonders bevor- zugt für Phenyl oder Naphthyl, wobei diese Arylgruppen im Falle einer Substitution im Allgemeinen 1 , 2, 3, 4 oder 5, vorzugsweise 1 , 2 oder 3 und besonders bevorzugt 1 Substituenten, ausgewählt aus den Gruppen Alkyl, Alkoxy, Carboxyl, Carboxylat, Trifluormethyl, -SO3H, Sulfonat, NE1E2, Alkylen-NE1E2, Nitro, Cyano oder Halogen, tragen können.The term "heterocycloalkyl" in the context of the present invention comprises saturated, cycloaliphatic groups having generally 4 to 7, preferably 5 or 6, ring atoms in which 1 or 2 of the ring carbon atoms are selected by heteroatoms, preferably selected from the elements oxygen, nitrogen and sulfur, are substituted and which may optionally be substituted, wherein in the case of a substitution, these heterocycloaliphatic groups 1, 2 or 3, preferably 1 or 2, particularly preferably 1 substituent selected from alkyl, aryl, COOR f , COO " M + and NE 1 e 2, preferably alkyl, can carry. Examples of such heterocycloaliphatic Grup¬ are groups pyrrolidinyl, piperidinyl, 2,2,6,6-tetramethyl piperidinyl, imidazolidinyl, pyramidal zolidinyl, oxazolidinyl, Morpholidinyl, thiazolidinyl, isothiazolidinyl, isoxazolidinyl, Piperazinyl, tetrahydrothiophenyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl. The term "aryl" for the purposes of the present invention includes unsubstituted as well as substituted aryl groups, and is preferably phenyl, ToIyI, XyIyI, mesityl, naphthyl, fluorenyl, anthracenyl, phenanthrenyl or naphthacenyl, more preferably phenyl or naphthyl, said Aryl groups in the case of a substitution in general 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent selected from the groups alkyl, alkoxy, carboxyl, carboxylate, trifluoromethyl, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , nitro, cyano or halogen.
Der Ausdruck "Hetaryl" umfasst im Sinne der vorliegenden Erfindung unsubstituierte oder substituierte, heterocycloaromatische Gruppen, vorzugsweise die Gruppen Pyri- dyl, Chinolinyl, Acridinyl, Pyridazinyl, Pyrimidinyl, Pyrazinyl, sowie die Untergruppe der "Pyrrolgruppe", wobei diese heterocycloaromatischen Gruppen im Falle einer Substitu- tion im Allgemeinen 1 , 2 oder 3 Substituenten, ausgewählt aus den Gruppen Alkyl, Alkoxy, Carboxyl, Carboxylat, -SO3H, Sulfonat, NE1E2, Alkylen-NE1E2, Trifluormethyl oder Halogen, tragen können.The term "hetaryl" for the purposes of the present invention comprises unsubstituted or substituted heterocycloaromatic groups, preferably the groups pyridyl, quinolinyl, acridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and the subgroup of the "pyrrole group", these heterocycloaromatic groups in the case of Substitu tion generally 1, 2 or 3 substituents selected from the groups alkyl, alkoxy, carboxyl, carboxylate, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , trifluoromethyl or halogen, can carry.
Der Ausdruck "Pyrrolgruppe" steht im Sinne der vorliegenden Erfindung für eine Reihe unsubstituierter oder substituierter, heterocycloaromatischer Gruppen, die strukturell vom Pyrrolgrundgerüst abgeleitet sind und ein pyrrolisches Stickstoffatom im Hetero- cyclus enthalten, das kovalent mit anderen Atomen, beispielsweise einem Pnicogena- tom, verknüpft werden kann. Der Ausdruck "Pyrrolgruppe" umfasst somit die unsubsti- tuierten oder substituierten Gruppen Pyrrolyl, Imidazolyl, Pyrazolyl, Indolyl, Purinyl, Indazolyl, Benzotriazolyl, 1 ,2,3-Triazolyl, 1 ,3,4-Triazolyl und Carbazolyl, die im Falle einer Substitution im Allgemeinen 1 , 2 oder 3, vorzugsweise 1 oder 2, besonders be¬ vorzugt 1 Substituenten, ausgewählt aus den Gruppen Alkyl, Alkoxy, Acyl, Carboxyl, Carboxylat, -SO3H, Sulfonat, NE1E2, Alkylen-NE1E2, Trifluormethyl oder Halogen, tra¬ gen können. Eine bevorzugte substituierte Indolylgruppe ist die 3-Methyl-indolylgruppe.The term "pyrrole group" in the context of the present invention is a series of unsubstituted or substituted heterocycloaromatic groups which are structurally derived from the pyrrole skeleton and contain a pyrrole nitrogen atom in the heterocycle which is covalently linked to other atoms, for example a pnicogen atom can be. The term "pyrrole group" thus includes the unsubstituted or substituted groups pyrrolyl, imidazolyl, pyrazolyl, indolyl, purinyl, indazolyl, benzotriazolyl, 1, 2,3-triazolyl, 1, 3,4-triazolyl and carbazolyl, which in the case of Substitution in general 1, 2 or 3, preferably 1 or 2, particularly preferably 1 substituent selected from the groups alkyl, alkoxy, acyl, carboxyl, carboxylate, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , trifluoromethyl or halogen, tra¬ gene can. A preferred substituted indolyl group is the 3-methylindolyl group.
Dementsprechend umfasst der Ausdruck "Bispyrrolgruppe" im Sinne der vorliegenden Erfindung zweibindige Gruppen der FormelAccordingly, the term "bispyrrole group" for the purposes of the present invention includes divalent groups of the formula
Py-I-Py,Py-I-Py,
die zwei durch direkte chemische Bindung oder Alkylen-, Oxa-, Thio-, Imino-, SiIyI oder Alkyliminogruppen vermittelte Verknüpfung, verbundene Pyrrolgruppen enthalten, wie die Bisindoldiyl-Gruppe der Formel the two linked by direct chemical bonding or alkylene, oxa, thio, imino, SiIyI or alkylimino groups, linked pyrrole groups, such as the bisindolediyl group of the formula
als Beispiel für eine Bispyrrolgruppe, die zwei direkt verknüpfte Pyrrolgruppen, in die¬ sem Falle Indolyl, enthält, oder die Bispyrroldiylmethan-Gruppe der Formelas an example of a bispyrrole group which contains two directly linked pyrrole groups, in which case indolyl, or the bispyrrolidinylmethane group of the formula
als Beispiel für eine Bispyrrolgruppe, die zwei über eine Methylengruppe verknüpfte Pyrrolgruppen, in diesem Falle Pyrrolyl, enthält. Wie die Pyrrolgruppen können auch die Bispyrrolgruppen unsubstituiert oder substituiert sein und im Falle einer Substitution pro Pyrrolgruppeneinheit im Allgemeinen 1 , 2 oder 3, vorzugsweise 1 oder 2, insbe¬ sondere 1 Substituenten, ausgewählt aus Alkyl, Alkoxy, Carboxyl, Carboxylat, -SO3H, Sulfonat, NE1E2, Alkylen-NE1E2, Trifluormethyl oder Halogen, tragen, wobei bei diesen Angaben zur Anzahl möglicher Substituenten die Verknüpfung der Pyrrolgruppenein- heiten durch direkte chemische Bindung oder durch die mittels der vorstehend genann¬ ten Gruppen vermittelte Verknüpfung nicht als Substitution betrachtet wird.as an example of a bispyrrole group containing two pyrrole groups linked via a methylene group, in this case pyrrolyl. Like the pyrrole groups, the bispyrrole groups may also be unsubstituted or substituted and in the case of a substitution per pyrrole group unit generally 1, 2 or 3, preferably 1 or 2, in particular 1 substituent selected from alkyl, alkoxy, carboxyl, carboxylate, -SO 3 H, sulfonate, NE 1 E 2 , alkylene-NE 1 E 2 , trifluoromethyl or halogen carry, wherein in these statements to the number of possible substituents linking the Pyrrolgruppenein- units by direct chemical bonding or by means of the genann¬ th groups mentioned above mediated linking is not considered a substitution.
Carboxylat und Sulfonat stehen im Rahmen dieser Erfindung vorzugsweise für ein De¬ rivat einer Carbonsäurefunktion bzw. einer Sulfonsäurefunktion, insbesondere für ein Metallcarboxylat oder -sulfonat, eine Carbonsäure- oder Sulfonsäureesterfunktion oder eine Carbonsäure- oder Sulfonsäureamidfunktion. Dazu zählen z. B. die Ester mit CrC4-Alkanolen, wie Methanol, Ethanol, n-Propanol, Isopropanol, n-Butanol, sec.-Butanol und tert.-Butanol. Dazu zählen weiterhin die primären Amide und deren N-Alkyl- und N.N-Dialkylderivate.Carboxylate and sulfonate in the context of this invention preferably represent a derivative of a carboxylic acid function or a sulfonic acid function, in particular a metal carboxylate or sulfonate, a carboxylic acid or sulfonic acid ester function or a carboxylic acid or sulfonic acid amide function. These include z. As the esters with CrC 4 alkanols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol and tert-butanol. These include the primary amides and their N-alkyl and NN-dialkyl derivatives.
Die obigen Erläuterungen zu den Ausdrücken "Alkyl", "Cycloalkyl", "Aryl", "Heterocyc- loalkyl" und "Hetaryl" gelten entsprechend für die Ausdrücke "Alkoxy", "Cycloalkoxy", "Aryloxy", "Heterocycloalkoxy" und "Hetaryloxy".The above explanations concerning the terms "alkyl", "cycloalkyl", "aryl", "heterocycloalkyl" and "hetaryl" apply correspondingly to the terms "alkoxy", "cycloalkoxy", "aryloxy", "heterocycloalkoxy" and "hetaryloxy ".
Der Ausdruck "Acyl" steht im Sinne der vorliegenden Erfindung für Alkanoyl- oder Aroylgruppen mit im Allgemeinen 2 bis 1 1 , vorzugsweise 2 bis 8 Kohlenstoffatomen, beispielsweise für die Acetyl-, Propanoyl-, Butanoyl-, Pentanoyl-, Hexanoyl-, Hepta- noyl-, 2-Ethylhexanoyl-, 2-Propylheptanoyl-, Benzoyl- oder Naphthoyl-Gruppe.The term "acyl" in the context of the present invention represents alkanoyl or aroyl groups having generally 2 to 11, preferably 2 to 8, carbon atoms, for example, the acetyl, propanoyl, butanoyl, pentanoyl, hexanoyl, heptanoyl, 2-ethylhexanoyl, 2-propylheptanoyl, benzoyl or naphthoyl group.
Die Gruppen NE1E2, NE4E5, NE7E8, NE10E11, NE13E14, NE16E17 und NE19E20 stehen vor- zugsweise für N,N-Dimethylamino, N.N-Diethylamino, N,N-Dipropylamino, N.N-Diisopropylamino, N,N-Di-n-butylamino, N,N-Di-t.-butylamino, N,N-Dicyclohexylamino oder N,N-Diphenylamino.The groups NE 1 E 2 , NE 4 E 5 , NE 7 E 8 , NE 10 E 11 , NE 13 E 14 , NE 16 E 17 and NE 19 E 20 are preferably N, N-dimethylamino, N, N-diethylamino , N, N-dipropylamino, N, N-diisopropylamino, N, N-di-n-butylamino, N, N-di-t-butylamino, N, N-dicyclohexylamino or N, N-diphenylamino.
Halogen steht für Fluor, Chlor, Brom und lod, bevorzugt für Fluor, Chlor und Brom.Halogen is fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine and bromine.
M+ steht für ein Kationäquivalent, d. h. für ein einwertiges Kation oder den einer positi¬ ven Einfachladung entsprechenden Anteil eines mehrwertigen Kations. Das Kation M+ dient lediglich als Gegenion zur Neutralisation negativ geladener Substituentengrup- pen, wie der COO- oder der Sulfonat-Gruppe und kann im Prinzip beliebig gewählt werden. Vorzugsweise werden deshalb Alkalimetall-, insbesondere Na+, K+-, Li+-Ionen oder Onium-Ionen, wie Ammonium-, Mono-, Di-, Tri-, Tetraalkylammonium-, Phospho- nium-, Tetraalkylphosphonium- oder Tetraarylphosphonium-Ionen verwendet.M + represents a cation equivalent, ie a monovalent cation or the proportion of a polyvalent cation corresponding to a positive single charge. The cation M + serves only as a counterion to the neutralization of negatively charged substituent groups, such as the COO or the sulfonate group, and can in principle be chosen arbitrarily. Preference is therefore given to alkali metal, in particular Na + , K + , Li + ions or onium ions, such as ammonium, mono-, di-, tri-, tetraalkylammonium, phosphonium, tetraalkylphosphonium or tetraarylphosphonium ions used.
Entsprechendes gilt für das Anionäquivalent X', das lediglich als Gegenion positiv ge- ladener Substituentengruppen, wie den Ammoniumgruppen, dient und beliebig gewählt werden kann unter einwertigen Anionen und den einer negativen Einfachladung ent¬ sprechenden Anteilen eines mehrwertigen Anions. Geeignete Anionen sind z. B. HaIo- genid-lonen X', wie Chlorid und Bromid. Bevorzugte Anionen sind Sulfat und Sulfonat, z. B. SO4 2", Tosylat, Trifluormethansulfonat und Methylsulfonat.The same applies to the anion equivalent X ' , which serves merely as a counterion of positively charged substituent groups, such as the ammonium groups, and can be chosen arbitrarily from monovalent anions and the portions of a polyvalent anion corresponding to a negative single charge. Suitable anions are z. For example, halide ion X ' such as chloride and bromide. Preferred anions are sulfate and sulfonate, e.g. As SO 4 2 " , tosylate, trifluoromethanesulfonate and methyl sulfonate.
Die Werte für x stehen für eine ganze Zahl von 1 bis 240, vorzugsweise für eine ganze Zahl von 3 bis 120.The values of x represent an integer of 1 to 240, preferably an integer of 3 to 120.
Kondensierte Ringsysteme können durch Anellierung verknüpfte (ankondensierte) aromatische, hydroaromatische und cyclische Verbindungen sein. Kondensierte Ring¬ systeme bestehen aus zwei, drei oder mehr als drei Ringen. Je nach der Verknüp¬ fungsart unterscheidet man bei kondensierten Ringsystemen zwischen einer ortho- Anellierung, d. h. jeder Ring hat mit jedem Nachbarring jeweils eine Kante, bzw. zwei Atome gemeinsam, und einer peri-Anellierung, bei der ein Kohlenstoffatom mehr als zwei Ringen angehört. Bevorzugt unter den kondensierten Ringsystemen sind ortho- kondensierte Ringsysteme.Condensed ring systems may be fused (fused) aromatic, hydroaromatic and cyclic compounds. Condensed ring systems consist of two, three or more than three rings. Depending on the type of linkage, in the case of fused ring systems a distinction is made between ortho-fusing, d. H. each ring has one edge or two atoms in common with each adjacent ring, and a peri-annulation in which one carbon atom belongs to more than two rings. Preferred among the fused ring systems are ortho-fused ring systems.
In einer ersten Ausführungsform stehen in den Phosphorchelatverbindungen der all¬ gemeinen Formel I die Substituenten Rα und Rßfür heteroatomhaltige Gruppen, die über ein gegebenenfalls substituiertes Stickstoffatom an das Phosphoratom gebunden sind, wobei Rα und Rp nicht miteinander verbunden sind. Bevorzugt stehen R" und Rß dann für über das pyrrolische Stickstoffatom an das Phosphoratom gebundene Pyr- rolgruppen. Die Bedeutung des Begriffs „Pyrrolgruppe" entspricht dabei der eingangs gegebenen Definition.In a first embodiment, in the phosphorochelate compounds of general formula I, the substituents R α and R β are heteroatom-containing groups which are bonded to the phosphorus atom via an optionally substituted nitrogen atom are where R α and R p are not connected to each other. Are preferably R "and R then ß rolgruppen for via the pyrrole nitrogen atom to the phosphorus atom bonded pyrrole. The meaning of the term" pyrrole "corresponds to the definition given above.
Bevorzugt sind Phosphorchelatverbindungen, in denen die Reste Rα und Rß unabhän¬ gig voneinander ausgewählt sind unter Gruppen der Formel ILa bis II. kPreference is given to phosphorus chelate compounds in which the radicals R α and R β are independently selected from among groups of the formula IIa to II. K
COOAIk COOAIk
(ILa) (ILb)(ILa) (ILb)
AIkOO COOAIkAIkOO COOAIk
(H-O) (ILd)(H-O) (ILd)
(ILe) (ll.f) (ii-g) (ILe) (II.f) (ii-g)
(ll.h) (H.i) (ll.k)(II.h) (H.i) (II.k)
worinwherein
Aik eine CrC4-Alkylgruppe ist undAik is a C r C 4 alkyl group and
Ra, Rb, Rc und Rd unabhängig voneinander für Wasserstoff, CrC4-Alkyl, Ci-C4-Alkoxy, Acyl, Halogen, Trifluormethyl, d-C4-Alkoxycarbonyl oder Carboxyl stehen.R a, R b, R c and R d are independently hydrogen, CrC 4 alkyl, Ci-C 4 alkoxy, acyl, halogen, trifluoromethyl, dC 4 alkoxycarbonyl or carboxyl.
Besonders bevorzugt steht wenigstens einer der Reste Rα und Rß für eine unsubstitu- ierte oder substituierte Indolylgruppe, die insbesondere ausgewählt ist unter den Grup¬ pen II. e bis II. i.Particularly preferably, at least one of the radicals R α and R β is an unsubstituted or substituted indolyl group which is in particular selected from groups II. E to II. I.
Bevorzugt sind in den Verbindungen der Formeln II. e bis II. i die Reste Ra und Rb unab- hängig voneinander ausgewählt unter Wasserstoff, CrC4-Alkyl, Ci-C4-Alkoxy und Ha¬ logen. Wenn wenigstens einer der Reste Ra und Rb für C1-C4-AIkVl steht, dann speziell für Methyl, Ethyl, n-Propyl, Isopropyl oder tert.-Butyl. Wenn wenigstens einer der Reste Ra und Rb für Ci-C4-Alkoxy steht, dann speziell für Methoxy, Ethoxy, n-Propyloxy, I- sopropyloxy oder tert.-Butyloxy. Wenn wenigstens einer der Reste Ra und Rb für HaIo- gen steht, dann speziell für Chlor.In the compounds of the formulas II. E to II.i, the radicals R a and R b are preferably independently of one another selected from hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and halogen. If at least one of the radicals R a and R b is C 1 -C 4 -alkyl, then especially methyl, ethyl, n-propyl, isopropyl or tert-butyl. If at least one of the radicals R a and R b is C 1 -C 4 -alkoxy, then especially methoxy, ethoxy, n-propyloxy, isopropyloxy or tert-butyloxy. If at least one of R a and R b is halogen, then especially chlorine.
In einer speziellen Ausführung stehen in den Verbindungen der Formeln II. e bis H.i die Reste Ra und Rb beide für Wasserstoff. In einer weiteren speziellen Ausführung steht in den Verbindungen der Formeln II. e bis H.i einer der Reste Ra und Rb für Wasserstoff und der andere für einen von Wasserstoff verschiedenen Rest, speziell Methyl, Metho¬ xy oder Chlor. Der von Wasserstoff verschiedene Rest befindet sich dann vorzugswei¬ se in der 4-, 5- oder 6-Position des Indolgerüsts.In a specific embodiment, in the compounds of the formulas II. E to Hi, the radicals R a and R b are both hydrogen. In a further specific embodiment, in the compounds of the formulas II. E to Hi, one of the radicals R a and R b is hydrogen and the other is a radical other than hydrogen, especially methyl, methoxy or chlorine. The radical other than hydrogen is then preferably in the 4-, 5- or 6-position of the indole skeleton.
Besonders bevorzugt stehen beide Reste Rαund Rß für eine solche unsubstituierte oder substituierte Indolylgruppe. Zur Veranschaulichung werden im Folgenden einige vorteilhafte Pyrrolgruppen aufge¬ listet:Particularly preferably, both radicals R α and R β stand for such an unsubstituted or substituted indolyl group. For illustrative purposes, some advantageous pyrrol groups are listed below:
/ /NVyCOOCH3 / / NVyCOOCH 3
(ll.ai) (Il.a2) (Il.b1) (Il.b2)(II.a.) (Il.a2) (Il.b1) (Il.b2)
OOCH3 OOCH 3
(II.C1 ) (II.C2) (ll.di)(II.C1) (II.C2) (ll.di)
(iι.d2) (iι.θi ) (II.Θ2)(iι.d2) (iι.θi) (II.Θ2)
(Il.e3) (Il.f1) (iι.f2) (Il.e3) (Il.f1) (iι.f2)
(Il.f3) (ii.gi) (ll.hi)(Il.f3) (ii.gi) (ll.hi)
(ii.ii) (ll.ki) (Il.k2)(ii.ii) (II.ki) (II.k2)
Besonders vorteilhaft ist die 3-Methylindolylgruppe (Skatolylgruppe) der Formel Il.f1. Hydroformylierungskatalysatoren auf Basis von Liganden, die eine oder mehrere 3-Methylindolylgruppe(n) an das Phosphoratom gebunden aufweisen, zeichnen sich durch eine besonders hohe Stabilität und somit besonders lange Katalysatorstandzei- ten aus.The 3-methylindolyl group (skatolyl group) of the formula II.f1 is particularly advantageous. Hydroformylation catalysts based on ligands which have one or more 3-methylindolyl group (s) attached to the phosphorus atom are distinguished by particularly high stability and thus particularly long catalyst residence times.
Besonders vorteilhaft sind weiterhin Phosphorchelatverbindungen, in denen die Reste Rα und Rß unabhängig voneinander ausgewählt sind unter: Also particularly advantageous are phosphorus chelate compounds in which the radicals R α and R β are selected independently of one another below:
In einer weiteren vorteilhaften Ausgestaltung der vorliegenden Erfindung stehen FT und Rß gemeinsam mit dem Phosphoratom, an das sie gebunden sind, für einen 5- bis 7-gliedrigen Heterocyclus, der zwei an das Phosphoratom gebundene Ringheteroato¬ me aufweist, wobei es sich bei mindestens einem dieser Ringheteroatome um ein ge¬ gebenenfalls substituiertes Stickstoffatom handelt. Vorzugsweise steht auch das zweite an das Phosphoratom gebundene Ringheteroatom für ein gegebenenfalls substituier¬ tes Stickstoff atom. Besonders bevorzugt bildet dann der Substituent Rα gemeinsam mit dem Substituenten Rß eine über die pyrrolischen Stickstoffatome an das Phosphoratom gebundene Bispyrrolgruppe. Die Bedeutung des Begriffs „Bispyrrolgruppe" entspricht dabei der eingangs gegebenen Definition.In a further advantageous embodiment of the present invention are FT and R ß together with the phosphorus atom to which they are attached, for a 5- to 7-membered heterocycle having two bonded to the phosphorus ring heteroatom me, wherein it is at least one of these ring heteroatoms is an optionally substituted nitrogen atom. The second ring heteroatom bonded to the phosphorus atom is preferably also an optionally substituted nitrogen atom. The substituent R α together with the substituent R β then particularly preferably forms a bispyrrole group bonded via the pyrrole nitrogen atoms to the phosphorus atom. The meaning of the term "bispyrrole group" corresponds to the definition given at the outset.
Vorzugsweise stehen Rα und Rß gemeinsam für einen 5- bis 7-gliedrigen Heterocyclus, der gegebenenfalls zusätzlich ein-, zwei-, drei- oder vierfach mit Cycloalkyl, Heterocyc- loaikyl, Aryl oder Hetaryl anelliert ist, wobei der Heterocyclus und, falls vorhanden, die anellierten Gruppen unabhängig voneinander je einen, zwei, drei oder vier Substituen¬ ten tragen können, die ausgewählt sind unter Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl, Hetaryl, Hydroxy, Thiol, Polyalkylenoxid, Polyalkylenimin, Alkoxy, Halogen, COOH, Carboxylat, SO3H, Sulfonat, NE4E5, NE4E5E6X", Nitro, Alkoxycarbonyl, Acyl und Cyano, worin E4, E5 und E6 jeweils gleiche oder verschiedene Reste, ausgewählt unter Was¬ serstoff, Alkyl, Cycloalkyl und Aryl bedeuten und X' für ein Anionäquivalent steht.Preferably, R α and R β together are a 5- to 7-membered heterocycle which is optionally additionally fi-, 2-, 3- or tetra-fused with cycloalkyl, heterocyclo- lauricyl, aryl or hetaryl, wherein the heterocycle and, if present, the fused groups independently of each other one, two, three or four substituents ten, which are selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine, alkoxy, halogen, COOH, carboxylate , SO 3 H, sulfonate, NE 4 E 5 , NE 4 E 5 E 6 X " , nitro, alkoxycarbonyl, acyl and cyano, wherein E 4 , E 5 and E 6 each represent identical or different radicals selected from hydrogen, alkyl, cycloalkyl and aryl and X 'is an anion equivalent.
Bevorzugt steht der Substituent Rα gemeinsam mit dem Substituenten Rß eine über das pyrrolische Stickstoffatom an das Phosphoratom gebundene Pyrrolgruppe enthal¬ tende zweibindige Gruppe der FormelPreferably, the substituent R α together with the substituent R ß is a divalent group of the formula ## STR5 ## which is bonded via the pyrrole nitrogen atom to the phosphorus atom
Py-I-W bilden,Form Py-I-W,
worinwherein
Py eine Pyrrolgruppe ist,Py is a pyrrole group,
I für eine chemische Bindung oder für O, S, SiR1R2,NR3 oder gegebenenfalls sub¬ stituiertes CrCio-Alkylen, bevorzugt CR4R5, steht,I represents a chemical bond or represents O, S, SiR 1 R 2 , NR 3 or optionally substituted C 1 -C 10 -alkylene, preferably CR 4 R 5 ,
W für Cycloalkyloxy oder -amino, Aryloxy oder -amino, Hetaryloxy oder -amino stehtW is cycloalkyloxy or amino, aryloxy or amino, hetaryloxy or amino
undand
R1, R2, R3, R4 und R5 unabhängig voneinander für Wasserstoff , Alkyl, Cycloalkyl, Hete- rocycloalkyl, Aryl oder Hetaryl stehen,R 1 , R 2 , R 3 , R 4 and R 5 independently of one another are hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl,
wobei die hierbei verwendeten Bezeichnungen die eingangs erläuterte Bedeutung ha¬ ben.the designations used here have the meaning explained above.
Geeignete zweibindige Gruppen der FormelSuitable divalent groups of the formula
Py-I-W sind z. B. Py-IW are z. B.
Bevorzugt sind Phosphorchelatverbindungen, worin Rα und Rß gemeinsam mit dem Phosphoratom, an das sie gebunden sind, für eine Gruppe der Formeln 11.1 bis II.3 Phosphor chelate compounds in which R α and R β together with the phosphorus atom to which they are bonded are preferred for a group of the formulas 11.1 to II.3
(IM) (II.2)(IM) (II.2)
(II.3)(II.3)
stehen, worinstand in which
R6 und R7 unabhängig voneinander für Wasserstoff, Alkyl, Cycloalkyl, Aryl, Hetaryl, Mesylat, Tosylat oder Trifluormethansulfonat stehen,R 6 and R 7 independently of one another are hydrogen, alkyl, cycloalkyl, aryl, hetaryl, mesylate, tosylate or trifluoromethanesulfonate,
R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 und R27 unabhängig voneinander für Wasserstoff, Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl, Hetaryl, W'COOR', W1COO-M+, W(SO3)R*, W'(SO3)-M+, W'PO3(Rf)(R9),R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 and R 27 independently of one another represent hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, W'COOR ', W 1 COO-M + , W (SO 3 ) R *, W' (SO 3 ) -M + , W'PO 3 (R f ) (R 9 ),
W'(PO3)2'(M+)2, W1NE13E14, W"(NE13E14E15)+X-, W'0Rf, W'SRf, (CHR9CH2O)xR', (CH2NE13)xRf, (CHaCH≥NE^xR', Halogen, Trifluormethyl, Nitro, Acyl oder Cyano stehen,W '(PO 3 ) 2' (M + ) 2 , W 1 NE 13 E 14 , W "(NE 13 E 14 E 15 ) + X-, W'0R f , W'SR f , (CHR 9 CH 2 O) x R ', (CH 2 NE 13 ) x R f , (CHaCH≥NE ^ xR', halogen, trifluoromethyl, nitro, acyl or cyano,
worinwherein
W' für eine Einfachbindung, ein Heteroatom, eine Heteroatom-haltige Gruppe oder eine zweiwertige verbrückende Gruppe mit 1 bis 20 Brückenatomen steht, Rf, E13, E14, E15 jeweils gleiche oder verschiedene Reste, ausgewählt unter Was¬ serstoff, Alkyl, Cycloalkyl oder Aryl bedeuten,W 'represents a single bond, a heteroatom, a heteroatom-containing group or a divalent bridging group having 1 to 20 bridging atoms, R f , E 13 , E 14 , E 15 are each the same or different radicals selected from hydrogen, alkyl, cycloalkyl or aryl,
Rg für Wasserstoff, Methyl oder Ethyl steht,R g is hydrogen, methyl or ethyl,
M+ für ein Kationäquivalent steht,M + is a cation equivalent,
X" für ein Anionäquivalent steht undX "stands for an anion equivalent and
x für eine ganze Zahl von 1 bis 240 steht,x is an integer from 1 to 240,
wobei jeweils zwei benachbarte Reste R8 bis R27 zusammen mit den Kohlenstoffato¬ men des Rings, an die sie gebunden sind, auch für ein kondensiertes Ringsystem mit 1 , 2 oder 3 weiteren Ringen stehen können.wherein in each case two adjacent radicals R 8 to R 27, together with the carbon atoms of the ring to which they are bonded, can also stand for a fused ring system having 1, 2 or 3 further rings.
Vorzugsweise sind in den Gruppen der Formel 11,1 die Reste R6 und R7 unabhängig voneinander ausgewählt unter Wasserstoff, C1-C4-AIkVl, insbesondere Methyl, Ethyl, n-Propyl, Isopropyl, n-Butyl und tert.-Butyl, Cs-Cβ-Cycloalkyl, insbesondere Cyclohexyl und Aryl, insbesondere Phenyl.Preferably, in the groups of formula 11.1, the radicals R 6 and R 7 are independently selected from hydrogen, C 1 -C 4 -AlkVl, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl , Cs-Cβ-cycloalkyl, in particular cyclohexyl and aryl, in particular phenyl.
Vorzugsweise stehen in den Gruppen der Formel 11.1 die Reste R8, R9, R10 und R11 für Wasserstoff.Preferably, in the groups of the formula 11.1, the radicals R 8 , R 9 , R 10 and R 11 are hydrogen.
Pnicogenchelatverbindungen der Formel I, worin Rα und Rß gemeinsam mit dem Phos- phoratom für eine chirale Gruppe der Formel 11.1 stehen, sind besonders bevorzugt.Pnicogen chelate compounds of the formula I in which R α and R β together with the phosphorus atom represent a chiral group of the formula II.1 are particularly preferred.
Vorzugsweise stehen in den Gruppen der Formel II.2 die Reste R12, R13, R14, R15, R16 und R17 für Wasserstoff.Preferably, in the groups of the formula II.2, the radicals R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen.
Des Weiteren bevorzugt sind Gruppen der Formel II.2, worin R12 und R13 und/oder R16 und R17 zusammen mit den Kohlenstoffatomen des Pyrrolrings, an die sie gebunden sind, für ein kondensiertes Ringsystem mit 1 , 2 oder 3 weiteren Ringen stehen. Bevor¬ zugt handelt es sich bei den weiteren Ringen um anellierte aromatischer Ringe. Bei den anellierten aromatischen Ringen handelt es sich bevorzugt um Benzol oder Naph- thalin. Anellierte Benzolringe sind vorzugsweise unsubstituiert oder weisen 1 , 2 oder 3, insbesondere 1 oder 2 Substituenten auf, die vorzugsweise ausgewählt sind unter Al¬ kyl, Alkoxy, Halogen, SO3H, Sulfonat, NE7E8, Alkylen-NE7E8, Trifluormethyl, Nitro, Car- boxyl, Alkoxycarbonyl, Acyl und Cyano. Anellierte Naphthaline sind vorzugsweise un¬ substituiert oder weisen im nicht anellierten Ring und/oder im anellierten Ring jeweils 1 , 2 oder 3, insbesondere 1 oder 2 der zuvor bei den anellierten Benzolringen genannten Substituenten auf. Bei den Substituenten der anellierten Aryle steht Alkyl vorzugsweise für C1-C4-AIkVl und insbesondere für Methyl, Isopropyl und tert.-Butyl. Alkoxy steht da¬ bei vorzugsweise für C1-C4-AIkOXy und insbesondere für Methoxy. Alkoxycarbonyl steht vorzugsweise für CrC4-Alkoxycarbonyl. Halogen steht dabei insbesondere für Fluor und Chlor.Further preferred are groups of formula II.2, wherein R 12 and R 13 and / or R 16 and R 17 together with the carbon atoms of the pyrrole ring to which they are attached, for a fused ring system having 1, 2 or 3 further rings stand. Preferably, the further rings are fused aromatic rings. The fused aromatic rings are preferably benzene or naphthalene. Anellierte benzene rings are preferably unsubstituted or have 1, 2 or 3, in particular 1 or 2 substituents, which are preferably selected from alkyl, alkoxy, halogen, SO 3 H, sulfonate, NE 7 E 8 , alkylene NE 7 E 8 , Trifluoromethyl, nitro, carboxyl, alkoxycarbonyl, acyl and cyano. Anellated naphthalenes are preferably unsubstituted or have in the non-fused ring and / or in the fused ring in each case 1, 2 or 3, in particular 1 or 2 of those previously mentioned in the fused benzene rings Substituents on. In the substituents of the fused aryls, alkyl is preferably C 1 -C 4 -alkyl and in particular methyl, isopropyl and tert-butyl. Alkoxy is preferably C 1 -C 4 -alkoxy and especially methoxy. Alkoxycarbonyl is preferably C r C 4 alkoxycarbonyl. Halogen is especially fluorine and chlorine.
Vorzugsweise stehen in den Gruppen der Formel II.3 die Reste R18, R19, R20, R21, R22, R23, R24, R25, R26 und R27 für Wasserstoff.In the groups of the formula II.3, the radicals R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 and R 27 are preferably hydrogen.
Des Weiteren bevorzugt sind Gruppen der Formel II.3, worin (R20 und R21) oder (R21 und R22) und/oder (R23 und R24) oder (R24 und R25) zusammen mit den Kohlenstoffato¬ men des Benzolrings, an die sie gebunden sind, für ein kondensiertes Ringsystem mit 1 , 2 oder 3 weiteren Ringen stehen. Bevorzugt handelt es sich bei den weiteren Ringen um anellierte aromatische Ringe. Bei den anellierten aromatischen Ringen handelt es sich bevorzugt um Benzol oder Naphthalin. Diese können gewünschtenfalls, wie zuvor für die Gruppen II.2 beschrieben, substituiert sein.Further preferred are groups of formula II.3, wherein (R 20 and R 21 ) or (R 21 and R 22 ) and / or (R 23 and R 24 ) or (R 24 and R 25 ) together with the Kohlenstoffato¬ of the benzene ring to which they are attached represent a fused ring system with 1, 2 or 3 further rings. The further rings are preferably fused aromatic rings. The fused aromatic rings are preferably benzene or naphthalene. If desired, these may be substituted as described above for groups II.2.
Zur Veranschaulichung werden im Folgenden einige vorteilhafte Gruppen 11.1 bis II.3 aufgelistet:As an illustration, some advantageous groups 11.1 to II.3 are listed below:
Vorzugsweise stehen Rγ und Rδ unabhängig voneinander für Substituenten, die nicht miteinander verbunden sind. Vorzugsweise sind Rγ und Rδ dann unabhängig vonein¬ ander ausgewählt unter Aryl- und Hetarylresten, die 1 , 2, 3, 4 oder 5 der zuvor genann¬ ten Substituenten aufweisen können. Bevorzugt steht wenigstens einer der Reste RY oder Rδ oder stehen beide dieser Reste für Aryl, welches einen, zwei oder drei Substi¬ tuenten aufweisen kann, die ausgewählt sind unter C1-C4-AIkYl, CrC4-Alkoxy und Kombinationen davon. Bevorzugte Reste RY und Rδ sind dann beispielsweise Phenyl, o-Tolyl, m-Xylyl und 3,5-Dimethyl-4-methoxyphenyl. Bei der verbrückenden Gruppe Y handelt es sich um eine chirale Gruppe, die vorzugs¬ weise wenigstens ein Chiralitätszentrum, eine Chiralitätsachse oder Chiralitätsebene aufweist.Preferably, R γ and R δ independently represent substituents which are not linked together. Preferably, R γ and R δ are then independently of one another selected from aryl and hetaryl radicals which may have 1, 2, 3, 4 or 5 of the abovementioned substituents. Preferably, at least one of R Y or R δ stands or both of these radicals are aryl, which may have one, two or three substituents which are selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and combinations thereof , Preferred radicals R Y and R δ are then, for example, phenyl, o-tolyl, m-xylyl and 3,5-dimethyl-4-methoxyphenyl. The bridging group Y is a chiral group which preferably has at least one chiral center, one chiral axis or chirality plane.
Vorzugsweise sind die verbrückenden Gruppen Y ausgewählt unter Gruppen der For¬ meln lll.a und III. bThe bridging groups Y are preferably selected from groups of formulas III.a and III. b
l.a)L.A)
(HLb)(HLB)
worinwherein
R1, R1', R", R"1, R"1, R"1', Rιv, Rlv', Rv, Rvι, Rv", RVI", Rix, Rx, RX1 und Rx" unabhängig von¬ einander für Wasserstoff, Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl, Hetaryl, Hydroxy, Thiol, Polyalkylenoxid, Polyalkylenimin, Alkoxy, Halogen, SO3H, Sulfo- nat, NE10E11, Alkylen-NE10E11, Trifluormethyl, Nitro, Alkoxycarbonyl, Carboxyl, Acyl oder Cyano stehen, worin E10 und E11 jeweils gleiche oder verschiedene Reste, ausgewählt unter Wasserstoff, Alkyl, Cycloalkyl und Aryl bedeuten. Des Weiteren bevorzugt steht Y für eine Gruppe der Formel lll.a, worin Rιv und Rv un¬ abhängig voneinander für CrC4-Alkyl oder CrC4-Alkoxy stehen. Vorzugsweise sind RN und Rv ausgewählt unter Methyl, Ethyl, Isopropyl, tert.-Butyl und Methoxy. Bevorzugt stehen in diesen Verbindungen R1, R", R111, Rvι, Rv" und Rvι" für Wasserstoff.R 1 , R 1 ' , R ", R" 1 , R " 1 , R"1' , R IV , R IV ' , R V , R VI , R V ", R VI ", R ix , R x , R X1 and R x "independently of one another, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine, alkoxy, halogen, SO 3 H nat, sulfo, NE 10 e 11 alkylene NE 10 E 11 , trifluoromethyl, nitro, alkoxycarbonyl, carboxyl, acyl or cyano, wherein E 10 and E 11 each represent identical or different radicals selected from hydrogen, alkyl, cycloalkyl and aryl. Furthermore, Y preferably represents a group of the formula IIIa, in which R IV and R V independently of one another represent C r C 4 -alkyl or C r C 4 -alkoxy. Preferably, R N and R v are selected from methyl, ethyl, isopropyl, tert -butyl and methoxy. Preferably in these compounds R 1 , R ", R 111 , R vι , R v " and R vι "are hydrogen.
Des Weiteren bevorzugt steht Y für eine Gruppe der Formel lll.a, worin R1 und Rvι" un¬ abhängig voneinander für CrC4-Alkyl oder Ci-C4-Alkoxy stehen. Besonders bevorzugt stehen R1 und Rvι" für tert.-Butyl. Besonders bevorzugt stehen in diesen Verbindungen R", R1", Rιv, Rv, Rvι, Rv" für Wasserstoff. Des Weiteren bevorzugt stehen in diesen Ver- bindungen R1" und Rvι unabhängig voneinander für C1-C4-AIkVl oder C1-C4-AIkOXy. Be¬ sonders bevorzugt sind RMI und Rvι unabhängig voneinander ausgewählt unter Methyl, Ethyl, Isopropyl, tert.-Butyl und Methoxy.Further, preferably Y is lll.a a group of the formula wherein R 1 and R VIII "un¬ interdependent for -C 4 alkyl or Ci-C 4 -alkoxy. Particularly preferably, R 1 and R VIII" for tert -butyl.. Particularly preferably, in these compounds, R ", R 1", R IV, R V, R VI, R v "is hydrogen. In addition, preferably, in these compounds, R 1" vι independently C1 and R 4 -alkyl or C 1 -C 4 -alkoxy. Particularly preferred are R MI and R vι are independently selected from methyl, ethyl, isopropyl, tert-butyl and methoxy.
Des Weiteren bevorzugt steht Y für eine Gruppe der Formel lll.a, worin R" und Rv" für Wasserstoff stehen. Bevorzugt stehen in diesen Verbindungen R1, R1", Rlv, Rv, Rvι und Rvι" unabhängig voneinander für CrC4-Alkyl oder C1-C4-AIkOXy. Besonders bevorzugt sind R1, R1", Rιv, Rv, Rvι und Rvι" unabhängig voneinander ausgewählt unter Methyl, Ethyl, Isopropyl, tert.-Butyl und Methoxy.Furthermore, Y is preferably a group of the formula IIIa, in which R "and R v " are hydrogen. Preferably, in these compounds, R 1, R "vι, R lv, R v, R and R VIII" 1 independently represent -C 4 alkyl or C 1 -C 4 -alkoxy. Particularly preferably, R 1 , R 1 ", R IV , R V , R Vι and R vι " are independently selected from methyl, ethyl, isopropyl, tert-butyl and methoxy.
Weiterhin bevorzugt steht Y für eine Gruppe der Formel III. b, worin R1 bis Rx" für Was¬ serstoff stehen.Furthermore, Y is preferably a group of the formula III. b, wherein R 1 to R x "are hydrogen.
Weiterhin bevorzugt steht Y für eine Gruppe der Formel III. b, worin R1 und Rx" unab¬ hängig voneinander für CrC4-Alkyl oder C1-C4-AIkOXy stehen. Insbesondere sind R1 und Rx" unabhängig voneinander ausgewählt unter Methyl, Ethyl, Isopropyl, tert.-Butyl, Methoxy und Alkoxycarbonyl, bevorzugt Methoxycarbonyl. Besonders bevorzugt ste¬ hen in diesen Verbindungen die Reste R11 bis Rxι für Wasserstoff.Furthermore, Y is preferably a group of the formula III. b, wherein R 1 and R x "unab¬ pending for C r C 4 alkyl or C 1 -C 4 -alkoxy are from each other. In particular, R 1 and R x 'are independently selected from methyl, ethyl, isopropyl, tert. Butyl, methoxy and alkoxycarbonyl, preferably methoxycarbonyl. Particularly preferably, in these compounds, the radicals R 11 to R xι are hydrogen.
Im Folgenden sind zur Veranschaulichung einige geeignete Liganden abgebildet:The following are illustrative of some suitable ligands:
'.3'.3
Ein weiterer Gegenstand der Erfindung ist ein chiraler Katalysator, umfassend wenigs¬ tens einen Komplex mit einem Metall der VIII. Nebengruppe des Periodensystems, der als Liganden wenigstens eine chirale Phosphorchelatverbindung, wie zuvor definiert, enthält.Another object of the invention is a chiral catalyst comprising wenigs¬ least a complex with a metal of the VIII. Subgroup of the Periodic Table, the at least one chiral phosphorochelate compound as defined above, as defined above.
Die erfindungsgemäßen und erfindungsgemäß eingesetzten chiralen Katalysatoren weisen wenigstens einen der zuvor beschriebenen Verbindungen als Liganden auf. Zusätzlich zu den zuvor beschriebenen Liganden können Sie noch wenigstens einen weiteren Liganden, der vorzugsweise ausgewählt ist unter Halogeniden, Aminen, Car- boxylaten, Acetylacetonat, Aryl- oder Alkylsulfonaten, Hydrid, CO, Olefinen, Dienen, Cycloolefinen, Nitrilen, N-haltigen Heterocyclen, Aromaten und Heteroaromaten, Ethern, PF3, Phospholen, Phosphabenzolen sowie ein-, zwei- und mehrzähnigen Phosphin-, Phosphinit-, Phosphonit-, Phosphoramidit- und Phosphitliganden aufwei¬ sen.The chiral catalysts according to the invention and used according to the invention have at least one of the compounds described above as ligands. In addition to the ligands described above, you can still at least one other ligand, which is preferably selected from halides, amines, carboxylates, acetylacetonate, aryl or alkyl sulfonates, hydride, CO, olefins, dienes, cycloolefins, nitriles, N-containing heterocycles , Aromatics and heteroaromatics, ethers, PF 3 , phospholes, phosphabenzenes and mono-, di- and polydentate phosphine, phosphinite, phosphonite, phosphoramidite and phosphite ligands aufwei¬ sen.
Bevorzugt handelt es sich bei dem Übergangsmetall um ein Metall der I., VI., VII. oder VIII. Nebengruppe des Periodensystems der Elemente. Besonders bevorzugt ist das Übergangsmetall ausgewählt unter den Metallen der VIII. Nebengruppe (d.h. Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, Pt). Insbesondere handelt es sich bei dem Übergangsmetall um Iridium, Ruthenium, Rhodium, Palladium oder Platin.The transition metal is preferably a metal of the I., VI., VII. Or VIII. Subgroup of the Periodic Table of the Elements. More preferably, the transition metal is selected from the metals of Group VIII (i.e., Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, Pt). In particular, the transition metal is iridium, ruthenium, rhodium, palladium or platinum.
Ein weiterer Gegenstand der Erfindung ist ein Verfahren zur Herstellung chiraler Ver¬ bindungen durch Umsetzung einer prochiralen Verbindung, die wenigstens eine ethy- lenisch ungesättigte Doppelbindung enthält, mit einem Substrat in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben. Dabei ist es lediglich erforderlich, dass wenigstens einer der eingesetzten Liganden oder die katalytisch aktive Spezies insge- samt chiral ist. Im Allgemeinen werden unter den Reaktionsbedingungen der einzelnen Verfahren zur Herstellung chiraler Verbindungen bestimmte Übergangsmetallkomplexe als katalytisch aktive Spezies gebildet. So werden beispielsweise unter Hydroformylie- rungsbedingungen aus den jeweils eingesetzten Katalysatoren oder Katalysatorvorstu¬ fen katalytisch aktive Spezies der allgemeinen Formel HxMy(CO)zLq gebildet, worin M für ein Übergangsmetall, L für eine Phosphorchelatverbindung und q, x, y, z für ganze Zahlen, abhängig von der Wertigkeit und Art des Metalls sowie der Bindigkeit des Li¬ ganden L, stehen. Vorzugsweise stehen z und q unabhängig voneinander mindestens für einen Wert von 1 , wie z. B. 1 , 2 oder 3. Die Summe aus z und q steht bevorzugt für einen Wert von 1 bis 5. Dabei können die Komplexe gewünschtenfalls zusätzlich noch mindestens einen der zuvor beschriebenen weiteren Liganden aufweisen.Another object of the invention is a process for preparing chiral Ver¬ compounds by reacting a prochiral compound containing at least one ethylenically unsaturated double bond, with a substrate in the presence of a chiral catalyst, as described above. All that is required is that at least one of the ligands used or the catalytically active species is entirely chiral. In general, certain transition metal complexes are formed as catalytically active species under the reaction conditions of the individual processes for producing chiral compounds. Thus, for example, catalytically active species of the general formula H x M y (CO) z L q are formed under hydroformylation conditions from the particular catalysts or catalyst precursors used, where M is a transition metal, L is a phosphorochelate compound and q, x, y , z are integers, depending on the valency and type of metal and the binding of ligand L, stand. Preferably z and q are independently of one another at least a value of 1, such. B. 1, 2 or 3. The sum of z and q is preferably from 1 to 5. In this case, the complexes may, if desired, additionally have at least one of the further ligands described above.
Die katalytisch aktive Spezies liegt vorzugsweise als homogen einphasige Lösung in einem geeigneten Lösungsmittel vor. Diese Lösung kann zusätzlich freien Liganden enthalten. Bevorzugt handelt es sich bei dem erfindungsgemäßen Verfahren zur Herstellung chi- raler Verbindungen um eine Hydrierung, Hydroformylierung, Hydrocyanierung, Carbo- nylierung, Hydroacylierung (intramolekular und intermolekular), Hydroamidierung, Hydroveresterung, Hydrosilylierung, Hydroborierung, Aminolyse (Hydroaminierung), Alkoholyse (Hydroxy-Alkoxy-Addition), Isomerisierung, Transferhydrierung, Metathese, Cyclopropanierung, Aldolkondensation, allylische Alkylierung oder eine [4+2]-Cycloaddition (Diels-Alder-Reaktion).The catalytically active species is preferably present as a homogeneous single-phase solution in a suitable solvent. This solution may additionally contain free ligands. The process according to the invention for the preparation of chiral compounds is preferably a hydrogenation, hydroformylation, hydrocyanation, carbonylation, hydroacylation (intramolecular and intermolecular), hydroamidation, hydroesterification, hydrosilylation, hydroboration, aminolysis (hydroamination), alcoholysis (hydroxylation). Alkoxy addition), isomerization, transfer hydrogenation, metathesis, cyclopropanation, aldol condensation, allylic alkylation, or a [4 + 2] cycloaddition (Diels-Alder reaction).
Besonders bevorzugt handelt es sich bei dem erfindungsgemäßen Verfahren zur Her- Stellung chiraler Verbindungen um eine 1 ,2-Addition, insbesondere eine Hydrierung oder eine 1-Hydro-2-Carbo-Addition. Im Rahmen dieser Erfindung bedeutet 1 ,2-Addition, dass eine Addition an die beiden benachbarten Atome einer C=X-Doppelbindung (X = C, Heteroatom) erfolgt. 1-Hydro-2-Carbo-Addition bezeichnet eine Additionsreaktion, bei der nach der Reaktion an ein Atom der Doppelbindung Wasserstoff und an das andere eine kohlenstoffatomhaltige Gruppe gebunden ist. Doppelbindungsisomerisierungen während der Addition sind dabei zugelassen. Im Rahmen dieser Erfindung soll mit 1-Hydro-2-Carbo-Addition bei unsymmetrischen Substraten nicht auch eine bevorzugte Addition des Kohlenstofffragmentes an das C2-Atom bezeichnet werden, da die Selektivität bezüglich der Orientierung der Addition in der Regel von dem zu addierenden Agens und dem eingesetzten Katalysator ab¬ hängig ist. "1-Hydro-2-Carbo-" ist insofern gleichbedeutend mit "1-Carbo-2-Hydro-".The process according to the invention for preparing chiral compounds is particularly preferably a 1,2-addition, in particular a hydrogenation or a 1-hydro-2-carboo addition. In the context of this invention 1,2-addition means that an addition to the two adjacent atoms of a C = X double bond (X = C, heteroatom) takes place. 1-Hydro-2-carbo-addition refers to an addition reaction in which, after the reaction, hydrogen is bonded to one atom of the double bond and a carbon atom-containing group is bonded to the other. Double bond isomerizations during addition are allowed. In the context of this invention, 1-hydro-2-carbo-addition in unsymmetrical substrates should not be referred to as a preferred addition of the carbon fragment to the C2 atom, since the selectivity with respect to the orientation of the addition of the generally to be added and depends on the catalyst used. "1-hydro-2-carbo-" is in this sense synonymous with "1-carbo-2-hydro-".
Die Reaktionsbedingungen der erfindungsgemäßen Verfahren zur Herstellung chiraler Verbindungen entsprechen, bis auf den eingesetzten chiralen Katalysator, in der Regel denen der entsprechenden asymmetrischen Verfahren. Geeignete Reaktoren und Re¬ aktionsbedingungen kann der Fachmann somit der einschlägigen Literatur zu dem je¬ weiligen Verfahren entnehmen und routinemäßig anpassen. Geeignete Reaktionstem¬ peraturen liegen im Allgemeinen in einem Bereich von -100 bis 500 0C, vorzugsweise in einem Bereich von -80 bis 250 0C. Geeignete Reaktionsdrücke liegen im Allgemei- nen in einem Bereich von 0,0001 bis 600 bar, bevorzugt von 0,5 bis 300 bar. Die Ver¬ fahren können im Allgemeinen kontinuierlich, semikontinuierlich oder diskontinuierlich erfolgen. Geeignete Reaktoren für die kontinuierliche Umsetzung sind dem Fachmann bekannt und werden z. B. in Ullmanns Enzyklopädie der technischen Chemie, Bd. 1 , 3. Aufl., 1951 , S. 743 ff. beschrieben. Geeignete druckfeste Reaktoren sind dem Fach- mann ebenfalls bekannt und werden z. B. in Ullmanns Enzyklopädie der technischen Chemie, Bd. 1 , 3. Auflage, 1951 , S. 769 ff. beschrieben.The reaction conditions of the processes according to the invention for the preparation of chiral compounds, except for the chiral catalyst used, generally correspond to those of the corresponding asymmetric processes. Suitable reactors and reaction conditions can thus be taken from the relevant literature on the respective method and routinely adapted by the person skilled in the art. Suitable temperatures Reaktionstem¬ are generally in a range from -100 to 500 0 C, preferably in a range from -80 to 250 0 C. Suitable reaction pressures are generally in a range of 0.0001 to 600 bar, preferably from 0.5 to 300 bar. The processes can generally be carried out continuously, semicontinuously or batchwise. Suitable reactors for the continuous reaction are known in the art and z. As described in Ullmann's Encyclopedia of Industrial Chemistry, Vol. 1, 3rd ed., 1951, p 743 ff. Suitable pressure-resistant reactors are also known in the art and are z. B. in Ullmann's Encyclopedia of Industrial Chemistry, Vol. 1, 3rd edition, 1951, p. 769 ff. Described.
Die erfindungsgemäßen Verfahren können in einem geeigneten, unter den jeweiligen Reaktionsbedingungen inerten Lösungsmittel durchgeführt werden. In der Regel ge- eignete Lösungsmittel sind z. B. Aromaten, wie Toluol und XyIoIe, Kohlenwasserstoffe oder Gemische von Kohlenwasserstoffen. Weiterhin geeignet sind halogenierte, insbe¬ sondere chlorierte Kohlenwasserstoffe, wie Dichlormethan, Chloroform oder 1 ,2-Dichlorethan. Weitere Lösungsmittel sind Ester aliphatischer Carbonsäuren mit Alkanolen, beispielsweise Essigester oder Texanol®, Ether wie tert.-Butylmethylether, Dioxan-1 ,4 und Tetrahydrofuran sowie Dimethylformamid. Bei ausreichend hydrophili- sierten Liganden können auch Alkohole, wie Methanol, Ethanol, n-Propanol, Isopropa- nol, n-Butanol, Isobutanol, Ketone, wie Aceton und Methylethylketon, etc., eingesetzt werden. Ferner können als Lösungsmittel auch so genannte "ionische Flüssigkeiten" verwendet werden. Hierbei handelt es sich um flüssige Salze, beispielsweise um N.N'-Dialkylimidazoliumsalze wie die N-Butyl-N'-methylimidazoliumsalze, Tetraalkyl- ammoniumsalze wie die Tetra-n-butylammoniumsalze, N-Alkylpyridiniumsalze wie die n-Butylpyridiniumsalze, Tetraalkylphosphoniumsalze wie die Trishexyl(tetradecyl)phosphoniumsalze, z. B. die Tetrafluoroborate, Acetate, Tetra- chloroaluminate, Hexafluorophosphate, Chloride und Tosylate. Als Lösungsmittel kann auch ein Edukt, Produkt oder Nebenprodukt der jeweiligen Reaktion eingesetzt wer¬ den.The processes according to the invention can be carried out in a suitable solvent which is inert under the respective reaction conditions. In general, suitable solvents are z. As aromatics, such as toluene and xylene, hydrocarbons or mixtures of hydrocarbons. Also suitable are halogenated, in particular chlorinated hydrocarbons, such as dichloromethane, chloroform or 1, 2-dichloroethane. Further solvents are esters of aliphatic carboxylic acids with alkanols, for example ethyl acetate or Texanol®, ethers, such as tert-butyl methyl ether, dioxane-1, 4 and tetrahydrofuran, and dimethylformamide. If the ligands are sufficiently hydrophilized, it is also possible to use alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, ketones, such as acetone and methyl ethyl ketone, etc. Further, as a solvent and so-called "ionic liquids" can be used. These are liquid salts, for example N, N'-dialkylimidazolium salts, such as the N-butyl-N'-methylimidazolium salts, tetraalkylammonium salts, such as the tetra-n-butylammonium salts, N-alkylpyridinium salts, such as the n-butylpyridinium salts, and tetraalkylphosphonium salts, such as Trishexyl (tetradecyl) phosphonium salts, e.g. As the tetrafluoroborates, acetates, tetrachloroaluminates, hexafluorophosphates, chlorides and tosylates. The solvent used may also be a starting material, product or by-product of the particular reaction.
Als prochirale ethylenisch ungesättigte Verbindungen für das erfindungsgemäße Ver¬ fahren kommen prinzipiell alle prochiralen Verbindungen in Betracht, welche eine oder mehrere ethylenisch ungesättigte Kohlenstoff-Kohlenstoff- oder Kohlenstoff-Suitable prochiral ethylenically unsaturated compounds for the process according to the invention are in principle all prochiral compounds which contain one or more ethylenically unsaturated carbon-carbon or carbonyl groups.
Heteroatom-Doppelbindungen enthalten. Dazu zählen allgemein prochirale Olefine (Hydroformylierung, intermolekulare Hydroacylierung, Hydrocyanierung, Hydrosilylie- rung, Carbonylierung, Hydroamidierung, Hydroveresterung, Aminolyse, Alkoholyse, Cyclopropanierung, Hydroborierung, Diels-Alder-Reaktion, Metathese), unsubstituierte und substituierte Aldehyde (intramolekulare Hydroacylierung, Aldolkondensation, allyli- sche Alkylierung), Ketone (Hydrierung, Hydrosilylierung, Aldolkondensation, Transfer¬ hydrierung, allylische Alkylierung) und Imine (Hydrierung, Hydrosilylierung, Transfer¬ hydrierung, Mannich-Reaktion).Heteroatom double bonds included. These include in general prochiral olefins (hydroformylation, intermolecular hydroacylation, hydrocyanation, hydrosilylation, carbonylation, hydroamidation, hydroesterification, aminolysis, alcoholysis, cyclopropanation, hydroboration, Diels-Alder reaction, metathesis), unsubstituted and substituted aldehydes (intramolecular hydroacylation, aldol condensation, allylic alkylation), ketones (hydrogenation, hydrosilylation, aldol condensation, transfer hydrogenation, allylic alkylation) and imines (hydrogenation, hydrosilylation, transfer hydrogenation, Mannich reaction).
Geeignete prochirale ethylenisch ungesättigte Olefine sind allgemein Verbindungen der FormelSuitable prochiral ethylenically unsaturated olefins are generally compounds of the formula
RC RDRC RD
worin RA und RB und/oder Rc und RD für Reste unterschiedlicher Definition stehen. Es versteht sich von selbst, dass zur erfindungsgemäßen Herstellung chiraler Verbindun¬ gen auch die mit der prochiralen ethylenisch ungesättigten Verbindung umgesetzten Substrate sowie unter Umständen auch die Stereoselektivität bezüglich der Anlagerung eines bestimmten Substituenten an ein bestimmtes C-Atom der C-C-Doppelbindung so gewählt werden, das zumindest ein chirales Kohlenstoffatom resultiert.wherein R A and R B and / or R c and R D are radicals of different definitions. It goes without saying that for the production according to the invention of chiral compounds, those reacted with the prochiral ethylenically unsaturated compound Substrates and possibly also the stereoselectivity with respect to the addition of a particular substituent to a particular carbon atom of the CC double bond can be chosen so that at least one chiral carbon atom results.
Vorzugsweise sind RA, RB, Rc und R.D unter Beachtung der vorgenannten Bedingung unabhängig voneinander ausgewählt unter Wasserstoff, Alkyl, Cycloalkyl, Heterocyclo- alkyl, Aryl, Hetaryl, Alkoxy, Cycloalkoxy, Heterocycloalkoxy, Aryloxy, Hetaryloxy, Hydroxy, Thiol, Polyalkylenoxid, Polyalkylenimin, COOH, Carboxylat, SO3H, Sulfonat, NE16E17, NE16E17E18X', Halogen, Nitro, Acyl, Acyloxy oder Cyano, worin E16, E17 und E18 jeweils gleiche oder verschiedene Reste, ausgewählt unter Wasserstoff, Alkyl, Cyc¬ loalkyl, oder Aryl bedeuten und X- für ein Anionäquivalent steht,Preferably, R A, R B, R c and R D in compliance with the above-mentioned condition is independently selected from hydrogen, alkyl, cycloalkyl, heterocyclo alkyl, aryl, hetaryl, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy, hetaryloxy, hydroxy, thiol , Polyalkylene oxide, polyalkyleneimine, COOH, carboxylate, SO 3 H, sulfonate, NE 16 E 17 , NE 16 E 17 E 18 X ' , halogen, nitro, acyl, acyloxy or cyano, wherein E 16 , E 17 and E 18 are each the same or different radicals selected from among hydrogen, alkyl, cycloalkyl, or aryl and X- is an anion equivalent,
wobei die Alkylreste 1, 2, 3, 4, 5 oder mehr Substituenten, ausgewählt unter Cycloalkyl, Heterocycloalkyl, Aryl, Hetaryl, Alkoxy, Cycloalkoxy, Heterocycloalkoxy, Aryloxy, Heta- ryloxy, Hydroxy, Thiol, Polyalkylenoxid, Polyalkylenimin, COOH, Carboxylat, SO3H, Sulfonat, NE19E20, NE19E20E21X', Halogen, Nitro, Acyl, Acyloxy oder Cyano aufweisen können, worin E19, E20 und E21 jeweils gleiche oder verschiedene Reste, ausgewählt unter Wasserstoff, Alkyl, Cycloalkyl, oder Aryl bedeuten und X' für ein Anionäquivalent steht,where the alkyl radicals have 1, 2, 3, 4, 5 or more substituents selected from cycloalkyl, heterocycloalkyl, aryl, hetaryl, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy, hetaryloxy, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine, COOH, carboxylate, SO 3 H, sulfonate, NE 19 E 20 , NE 19 E 20 E 21 X ' , halogen, nitro, acyl, acyloxy or cyano, wherein E 19 , E 20 and E 21 are each the same or different radicals selected from hydrogen , Alkyl, cycloalkyl, or aryl and X 'is an anion equivalent,
und wobei die Cycloalkyl-, Heterocycloalkyl-, Aryl- und Hetarylreste RA, RB, Rc und RD jeweils 1 , 2, 3, 4, 5 oder mehr Substituenten aufweisen können, die ausgewählt sind unter Alkyl und den zuvor für die Alkylreste RA, RB, Rc und RD genannten Substituen¬ ten, oderand wherein the cycloalkyl, heterocycloalkyl, aryl and hetaryl radicals R A , R B , R c and R D may each have 1, 2, 3, 4, 5 or more substituents selected from alkyl and those previously described for the Alkyl substituents R A , R B , R c and R D substituents th, or
zwei oder mehr der Reste RA, RB, Rc und RD zusammen mit der C-C-Doppelbindung, an die sie gebunden sind, für eine mono- oder polycyclische Verbindung stehen.two or more of R A , R B , R c and R D together with the CC double bond to which they are attached represent a mono- or polycyclic compound.
Geeignete prochirale Olefine sind Olefine mit mindestens 4 Kohlenstoffatomen und endständigen oder innenständigen Doppelbindungen, die geradkettig, verzweigt oder von cyclischer Struktur sind.Suitable prochiral olefins are olefins having at least 4 carbon atoms and terminal or internal double bonds which are straight-chain, branched or cyclic in structure.
Geeignete α-Olefine sind z. B. 1 -Buten, 1-Penten, 1 -Hexen, 1-Hepten, 1-Octen, 1-Nonen, 1-Decen, 1-Undecen, 1-Dodecen, 1-Octadecen etc.Suitable α-olefins are, for. 1-butene, 1-pentene, 1-hexene, 1-heptene, 1-octene, 1-nonene, 1-decene, 1-undecene, 1-dodecene, 1-octadecene, etc.
Geeignete lineare (geradkettige) interne Olefine sind vorzugsweise C4-C2o-Olefine, wie 2-Buten, 2-Penten, 2-Hexen, 3-Hexen, 2-Hepten, 3-Hepten, 2-Octen, 3-Octen, 4-Octen etc. Geeignete verzweigte, interne Olefine sind vorzugsweise C4-C2o-Olefine, wie 2-Methyl- 2-buten, 2-Methyl-2-penten, 3-Methyl-2-penten, verzweigte, interne Hepten-Gemische, verzweigte, interne Octen-Gemische, verzweigte, interne Nonen-Gemische, verzweig¬ te, interne Decen-Gemische, verzweigte, interne Undecen-Gemische, verzweigte, in- terne Dodecen-Gemische etc.Suitable linear (straight-chain) internal olefins are preferably C 4 -C 2 o-olefins, such as 2-butene, 2-pentene, 2-hexene, 3-hexene, 2-heptene, 3-heptene, 2-octene, 3-octene , 4-octene etc. Suitable branched internal olefins are preferably C 4 -C 2 o-olefins such as 2-methyl butene-2, 2-methyl-2-pentene, 3-methyl-2-pentene, branched, internal heptene mixtures, branched, internal octene mixtures, branched, internal nonene mixtures, branched, internal decene mixtures, branched, internal undecene mixtures, branched, internal dodecene mixtures, etc.
Geeignete zu hydroformylierende Olefine sind weiterhin C5-C8-Cycloalkene, wie Cyclopenten, Cyclohexen, Cyclohepten, Cycloocten und deren Derivate, wie z. B. de¬ ren C1-C20-Alkylderivate mit 1 bis 5 Alkylsubstituenten.Suitable olefins to be hydroformylated are furthermore C 5 -C 8 -cycloalkenes, such as cyclopentene, cyclohexene, cycloheptene, cyclooctene and their derivatives, such as. B. de¬ Ren C 1 -C 20 alkyl derivatives having 1 to 5 alkyl substituents.
Geeignete zu hydroformylierende Olefine sind weiterhin Vinylaromaten, wie Styrol, α-Methylstyrol, 4-lsobutylstyrol etc., 2-Vinyl-6-methoxynaphthalin, (3-Ethenylphenyl)- phenylketon, (4-Ethenylphenyl)-2-thienylketon, 4-Ethenyl-2-fluorbiphenyl, 4-(1 ,3-Dihydro-1-oxo-2H-isoindol-2-yl)styrol, 2-Ethenyl-5- benzoylthiophen, (3-Ethenylphenyl)phenylether, Propenylbenzol, 2-Propenylphenol, lsobutyl-4-propenylbenzol, Phenylvinylether und cyclische Enamide, z. B. 2,3-Diydro-1 ,4-oxazine, wie 2,3-Diydro-4-tert.-Butoxycarbonyl-1,4-oxazin. Geeignete zu hydroformylierende Olefine sind weiterhin α,ß-ethylenisch ungesättigte Mono- und/oder Dicarbonsäuren, deren Ester, Halbester und Amide, wie Acrylsäure, Methacrylsäure, Maleinsäure, Fumarsäure, Crotonsäure, Itaconsäure, 3-Pentensäuremethylester,Suitable olefins to be hydroformylated are furthermore vinylaromatics, such as styrene, α-methylstyrene, 4-isobutylstyrene, etc., 2-vinyl-6-methoxynaphthalene, (3-ethenylphenyl) phenylketone, (4-ethenylphenyl) -2-thienyl ketone, 4-ethenyl -2-fluorobiphenyl, 4- (1,3-dihydro-1-oxo-2H-isoindol-2-yl) styrene, 2-ethenyl-5-benzoylthiophene, (3-ethenylphenyl) phenyl ether, propenylbenzene, 2-propenylphenol, isobutyl 4-propenylbenzene, phenyl vinyl ethers and cyclic enamides, e.g. For example, 2,3-dihydro-1, 4-oxazines, such as 2,3-dihydro-4-tert-butoxycarbonyl-1,4-oxazine. Suitable olefins to be hydroformylated are furthermore α, β-ethylenically unsaturated mono- and / or dicarboxylic acids, their esters, monoesters and amides, such as acrylic acid, methacrylic acid, maleic acid, fumaric acid, crotonic acid, itaconic acid, methyl 3-pentenoate,
4-Pentensäuremethylester, Ölsäuremethylester, Acrylsäuremethylester, Methacrylsäu- remethylester, ungesättigte Nitrile, wie 3-Pentennitril, 4-Pentennitril, Acrylnitril, Vinyl- ether, wie Vinylmethylether, Vinylethylether, Vinylpropylether etc., Vinylchlorid, AIIyI- chlorid, C3-C2o-Alkenole, -Alkendiole und -Alkadienole, wie Allylalkohol, Hex-1-en-4-ol, Oct-1-en-4-ol, 2,7-Octadienol-1. Geeignete Substrate sind weiterhin Di- oder Polyene mit isolierten oder konjugierten Doppelbindungen. Dazu zählen z. B. 1 ,3-Butadien, 1 ,4-Pentadien, 1 ,5-Hexadien, 1 ,6-Heptadien, 1 ,7-Octadien, 1 ,8-Nonadien, 1 ,9-Decadien, 1 ,10-Undecadien, 1 ,11-Dodecadien, 1 ,12-Tridecadien, 1 ,13-Tetradecadien, Vinylcyclohexen, Dicyclopentadien, 1 ,5,9-Cyclooctatrien sowie Butadienhomo- und -copolymere.4-pentenoic acid methyl ester, oleic acid methyl ester, methyl acrylate, methacrylic acid methyl ester, unsaturated nitriles such as 3-pentenenitrile, 4-pentenenitrile, acrylonitrile, vinyl ethers such as vinylmethyl ether, vinyl ethyl ether, vinyl propyl ether, etc., vinyl chloride, AIIyI- chloride, C 3 -C 2 o-alkenols, alkenediols and alkadienols such as allyl alcohol, hex-1-en-4-ol, oct-1-en-4-ol, 2,7-octadienol-1. Suitable substrates are also di- or polyenes with isolated or conjugated double bonds. These include z. B. 1, 3-butadiene, 1, 4-pentadiene, 1, 5-hexadiene, 1, 6-heptadiene, 1, 7-octadiene, 1, 8-nonadiene, 1, 9-decadiene, 1, 10-undecadiene, 1, 11-dodecadiene, 1, 12-tridecadiene, 1, 13-tetradecadiene, vinylcyclohexene, dicyclopentadiene, 1, 5,9-cyclooctatriene and Butadienhomo- and copolymers.
Weitere als Synthesebausteine wichtige prochirale ethylenisch ungesättigte Verbin¬ dungen sind z. B. p-lsobutylstyrol, 2-Vinyl-6-methoxynaphthalin, (3-Ethenylphenyl)- phenylketon, (4-Ethenylphenyl)-2-thienylketon, 4-Ethenyl-2-fluorbiphenyl, 4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)styrol, 2-Ethenyl-5- benzoylthiophen, (3-Ethenylphenyl)phenylether, Propenylbenzol, 2-Propenylphenol, Isobu- tyl-4-propenylbenzol, Phenylvinylether und cyclische Enamide, z. B. 2,3-Diydro-1 ,4-oxazine, wie 2,3-Diydro-4-tert.-Butoxycarbonyl-1 ,4-oxazin. Die zuvor genannten Olefine können einzeln oder in Form von Gemischen eingesetzt werden.Other prochiral ethylenically unsaturated compounds which are important as synthesis building blocks are, for example, P-isobutylstyrene, 2-vinyl-6-methoxynaphthalene, (3-ethenylphenyl) phenylketone, (4-ethenylphenyl) -2-thienyl ketone, 4-ethenyl-2-fluorobiphenyl, 4- (1,3-dihydro-1 -oxo-2H-isoindol-2-yl) styrene, 2-ethenyl-5-benzoylthiophene, (3-ethenylphenyl) phenyl ether, propenylbenzene, 2-propenylphenol, isobutyl-4-propenylbenzene, phenylvinyl ethers and cyclic enamides, e.g. For example, 2,3-dihydro-1, 4-oxazines, such as 2,3-dihydro-4-tert-butoxycarbonyl-1, 4-oxazine. The aforementioned olefins can be used individually or in the form of mixtures.
Nach einer bevorzugten Ausführungsform werden die erfindungsgemäßen und erfin- dungsgemäß eingesetzten chiralen Katalysatoren in situ in dem für die Reaktion einge¬ setzten Reaktor hergestellt. Gewünschtenfalls können die erfindungsgemäßen Katalysatoren jedoch auch separat hergestellt und nach üblichen Verfahren isoliert werden. Zur in situ-Herstellung der erfindungsgemäßen Katalysatoren kann man z. B. wenigstens einen erfindungsgemäß eingesetzten Liganden, eine Verbindung oder einen Komplex eines Übergangsmetalls, gegebenenfalls wenigstens einen weiteren zusätzlichen Liganden und gegebenenfalls ein Aktivierungsmittel in einem inerten Lösungsmittel unter den Bedingungen der jeweiligen Reaktion (z. B. unter Hydroformylierungsbedingungen, Hydrocyanierungsbedingungen, etc.) umsetzen. Geeignete Aktivierungsmittel sind z. B. Brönsted-Säuren, Lewis-Säuren, wie z. B. BF3, AICI3, ZnCI2, und Lewis-Basen.According to a preferred embodiment, the chiral catalysts according to the invention and used according to the invention are prepared in situ in the reactor used for the reaction. If desired, however, the catalysts according to the invention can also be prepared separately and isolated by customary processes. For in situ preparation of the catalysts of the invention can be z. B. at least one ligand used in the invention, a compound or complex of a transition metal, optionally at least one further additional ligand and optionally an activating agent in an inert solvent under the conditions of the reaction (eg., Under hydroformylation, Hydrocyanierungsbedingungen, etc.) , Suitable activating agents are, for. B. Bronsted acids, Lewis acids, such as. B. BF 3 , AICI 3 , ZnCl 2 , and Lewis bases.
Als Katalysator-Precursor geeignet sind ganz allgemein Übergangsmetalle, Über¬ gangsmetallverbindungen und Übergangsmetallkomplexe.Suitable catalyst precursors are very generally transition metals, transition metal compounds and transition metal complexes.
Geeignete Rhodiumverbindungen oder -komplexe sind z. B. Rhodium(ll)- und Rhodi- um(lll)-salze, wie Rhodium(lll)-chlorid, Rhodium(lll)-nitrat, Rhodium(lll)-sulfat, Kalium- Rhodiumsulfat, Rhodium(ll)- bzw. Rhodium(lll)-carboxylat, Rhodium(ll)- und Rhodi- um(lll)-acetat, Rhodium(lll)-oxid, Salze der Rhodium(lll)-säure, Trisammonium- hexachlororhodat(lll) etc. Weiterhin eignen sich Rhodiumkomplexe, wie Rh4(CO)12, Rhodiumbiscarbonylacetylacetonat, Acetylacetonatobisethylenrhodium(l) etc.Suitable rhodium compounds or complexes are, for. Rhodium (II) and rhodium (III) salts, such as rhodium (III) chloride, rhodium (III) nitrate, rhodium (III) sulfate, potassium rhodium sulfate, rhodium (II) or Rhodium (III) carboxylate, rhodium (II) and rhodium (III) acetate, rhodium (III) oxide, salts of rhodium (III) acid, trisammonium hexachlororhodate (III), etc. Furthermore, rhodium complexes are suitable such as Rh 4 (CO) 12 , rhodiumbiscarbonylacetylacetonate, acetylacetonato-bis-ethyl rhodium (I), etc.
Ebenfalls geeignet sind Rutheniumsalze oder -Verbindungen. Geeignete Ruthenium¬ salze sind beispielsweise Ruthenium(lll)chlorid, Ruthenium(IV)-, Ruthenium(VI)- oder Ruthenium(VIII)oxid, Alkalisalze der Rutheniumsauerstoffsäuren wie K2RuO4 oder KRuO4 oder Komplexverbindungen, wie z. B. RuHCI(CO)(PPh3)3, (Ru(p-Cymen)CI)2, (Ru(benzol)CI)2, (COD)Ru(methallyl)2, Ru(acac)3. Auch können die Metallcarbonyle des Rutheniums wie Trisrutheniumdodecacarbonyl oder Hexarutheniumoctadecacar- bonyl, oder Mischformen, in denen CO teilweise durch Liganden der Formel PR3 er¬ setzt sind, wie Ru(CO)3(PPh3)2, im erfindungsgemäßen Verfahren verwendet werden.Also suitable are ruthenium salts or compounds. Suitable ruthenium salts are, for example, ruthenium (III) chloride, ruthenium (IV), ruthenium (VI) or ruthenium (VIII) oxide, alkali salts of ruthenium oxygen acids such as K 2 RuO 4 or KRuO 4 or complex compounds, such as. B. RuHCl (CO) (PPh 3 ) 3 , (Ru (p-cymene) Cl) 2 , (Ru (benzene) Cl) 2 , (COD) Ru (methallyl) 2 , Ru (acac) 3 . It is also possible to use the metal carbonyls of ruthenium, such as trisruthenium dodecacarbonyl or hexaruthenium octadecacarbonyl, or mixed forms in which CO are partly replaced by ligands of the formula PR 3 , such as Ru (CO) 3 (PPh 3 ) 2 , in the process according to the invention.
Geeignete Eisenverbindungen sind z. B. Eisen(lll)acetat und Eisen(lll)nitrat sowie die Carbonylkomplexe des Eisens. Geeignete Nickelverbindungen sind Nickelfluorid und Nickelsulfat. Ein zur Herstellung eines Nickelkatalysators geeigneter Nickelkomplex ist z. B. Bis(1,5-cyclooctadien)- nickel(O).Suitable iron compounds are for. As iron (III) acetate and iron (III) nitrate and the carbonyl complexes of iron. Suitable nickel compounds are nickel fluoride and nickel sulfate. A suitable for the preparation of a nickel catalyst nickel complex is z. Bis (1,5-cyclooctadiene) nickel (O).
Geeignet sind weiterhin Carbonylkomplexe des Iridiums und Osmiums, Osmiumhalo¬ genide, Osmiumoctoat, Palladiumhydride und -halogenide, Platinsäure, Iridiumsulfat, etc.Also suitable are carbonyl complexes of iridium and osmium, osmium halides, osmium octoate, palladium hydrides and halides, platinic acid, iridium sulfate, etc.
Die genannten und weitere geeignete Übergangsmetallverbindungen und -komplexe sind im Prinzip bekannt und in der Literatur hinreichend beschrieben oder sie können vom Fachmann analog zu den bereits bekannten Verbindungen hergestellt werden.The above-mentioned and other suitable transition metal compounds and complexes are known in principle and adequately described in the literature or they can be prepared by the skilled artisan analogous to the already known compounds.
Im Allgemeinen liegt die Metallkonzentration im Reaktionsmedium in einem Bereich von etwa 1 bis 10000 ppm. Das Molmengenverhältnis von Monopnicogenligand zu Übergangsmetall liegt im Allgemeinen in einem Bereich von etwa 0,5:1 bis 1000:1 , vorzugsweise 1 :1 bis 500:1.In general, the metal concentration in the reaction medium is in a range of about 1 to 10,000 ppm. The molar ratio of monopnicogen ligand to transition metal is generally in the range of about 0.5: 1 to 1000: 1, preferably 1: 1 to 500: 1.
Geeignet ist auch der Einsatz von geträgerten Katalysatoren. Die zuvor beschriebenen Katalysatoren können dazu in geeigneter Weise, z. B. durch Anbindung über als An- kergruppen geeignete funktionelle Gruppen, Adsorption, Pfropfung, etc. an einen ge¬ eigneten Träger, z. B. aus Glas, Kieselgel, Kunstharzen, Polymeren etc., immobilisiert werden. Sie eignen sich dann auch für einen Einsatz als Festphasenkatalysatoren.Also suitable is the use of supported catalysts. The catalysts described above can be suitably, for. B. by attachment via suitable as anchor groups functional groups, adsorption, grafting, etc. to a ge suitable carrier, eg. Example of glass, silica gel, resins, polymers, etc., be immobilized. They are then also suitable for use as solid phase catalysts.
Nach einer ersten bevorzugten Ausführungsform handelt es sich bei dem erfindungs- gemäßen Verfahren um eine Hydrierung (1 ,2-H,H-Addition). So gelangt man durchIn a first preferred embodiment, the process according to the invention is a hydrogenation (1,2-H, H addition). How to get through
Umsetzung einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit Wasserstoff in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu entsprechenden chiralen Verbindungen mit einer Einfachbin¬ dung. Aus prochiralen Olefinen gelangt man zu chiralen kohlenstoffhaltigen Verbindun- gen, aus prochiralen Ketonen zu chiralen Alkoholen und aus prochiralen Iminen zu chiralen Aminen.Reacting a prochiral compound containing at least one ethylenically unsaturated double bond, with hydrogen in the presence of a chiral catalyst, as described above, to corresponding chiral compounds having a single bond. Prochiral olefins lead to chiral carbonaceous compounds, prochiral ketones to chiral alcohols, and prochiral imines to chiral amines.
Nach einer weiteren bevorzugten Ausführungsform handelt es sich bei dem erfin¬ dungsgemäßen Verfahren um eine Umsetzung mit Kohlenmonoxid und Wasserstoff, die im Folgenden als Hydroformylierung bezeichnet wird.According to a further preferred embodiment, the process according to the invention is a reaction with carbon monoxide and hydrogen, which is referred to below as hydroformylation.
Die Hydroformylierung kann in Gegenwart eines der zuvor genannten Lösungsmittel erfolgen. Das Molmengenverhältnis von Mono(pseudo)pnicogenligand zu Metall der VIII. Ne¬ bengruppe liegt im Allgemeinen in einem Bereich von etwa 1:1 bis 1000:1 , vorzugswei¬ se 2:1 bis 500:1.The hydroformylation can be carried out in the presence of one of the abovementioned solvents. The molar ratio of mono (pseudo) pnicogen ligand to metal of the VIII. Ne¬ bengruppe is generally in a range of about 1: 1 to 1000: 1, vorzugswei¬ se 2: 1 to 500: 1.
Bevorzugt ist ein Verfahren, das dadurch gekennzeichnet ist, dass der Hydroformylie- rungskatalysator in situ hergestellt wird, wobei man mindestens einen erfindungsge¬ mäß einsetzbaren Liganden, eine Verbindung oder einen Komplex eines Übergangs¬ metalls und gegebenenfalls ein Aktivierungsmittel in einem inerten Lösungsmittel unter den Hydroformylierungsbedingungen zur Reaktion bringt.Preference is given to a process which is characterized in that the hydroformylation catalyst is prepared in situ, at least one ligand which can be used according to the invention, a compound or a complex of a transition metal and optionally an activating agent in an inert solvent under the hydroformylation conditions brings to reaction.
Bei dem Übergangsmetall handelt es sich vorzugsweise um ein Metall der VIII. Neben¬ gruppe des Periodensystems der Elemente, besonders bevorzugt um Cobalt, Rutheni¬ um, Iridium, Rhodium und Palladium. Insbesondere wird Rhodium eingesetzt.The transition metal is preferably a metal of the VIII. Neben¬ group of the Periodic Table of the Elements, more preferably cobalt, ruthenium, iridium, rhodium and palladium. In particular, rhodium is used.
Die Zusammensetzung des im erfindungsgemäßen Verfahren eingesetzten Synthese¬ gases aus Kohlenmonoxid und Wasserstoff kann in weiten Bereichen variieren. Das molare Verhältnis von Kohlenmonoxid und Wasserstoff beträgt in der Regel etwa 5:95 bis 70:30, bevorzugt etwa 40:60 bis 60:40. Insbesondere bevorzugt wird ein molares Verhältnis von Kohlenmonoxid und Wasserstoff im Bereich von etwa 1 :1 eingesetzt.The composition of the synthesis gas used in the process according to the invention of carbon monoxide and hydrogen can vary within wide ranges. The molar ratio of carbon monoxide and hydrogen is usually about 5:95 to 70:30, preferably about 40:60 to 60:40. Particularly preferred is a molar ratio of carbon monoxide and hydrogen in the range of about 1: 1 is used.
Die Temperatur bei der Hydroformylierungsreaktion liegt im Allgemeinen in einem Be¬ reich von etwa 20 bis 180 0C, bevorzugt etwa 50 bis 150 0C. Im Allgemeinen liegt der Druck in einem Bereich von etwa 1 bis 700 bar, bevorzugt 1 bis 600 bar, insbesondere 1 bis 300 bar. Der Reaktionsdruck kann in Abhängigkeit von der Aktivität des einge- setzten erfindungsgemäßen Hydroformylierungskatalysators variiert werden. Im Allge¬ meinen erlauben die erfindungsgemäßen Katalysatoren auf Basis von phosphorhalti- gen Verbindungen eine Umsetzung in einem Bereich niedriger Drücke, wie etwa im Bereich von 1 bis 100 bar.The temperature during the hydroformylation reaction is generally in a range from about Be¬ 20 to 180 0 C, preferably about 50 to 150 0 C. In general, the pressure is in a range of about 1 to 700 bar, preferably from 1 to 600 bar, in particular 1 to 300 bar. The reaction pressure can be varied depending on the activity of the hydroformylation catalyst of the invention used. In general, the novel catalysts based on phosphorus-containing compounds allow a reaction in a range of low pressures, such as in the range of 1 to 100 bar.
Die erfindungsgemäß eingesetzten und die erfindungsgemäßen Hydroformylierungska- talysatoren lassen sich nach üblichen, dem Fachmann bekannten Verfahren vom Aus¬ trag der Hydroformylierungsreaktion abtrennen und können im Allgemeinen erneut für die Hydroformylierung eingesetzt werden.The hydroformylation catalysts according to the invention and the hydroformylation catalysts according to the invention can be separated off from the starting point of the hydroformylation reaction by customary methods known to the person skilled in the art and can generally be used again for the hydroformylation.
Die asymmetrische Hydroformylierung nach dem erfindungsgemäßen Verfahren zeich¬ net sich durch eine hohe Stereoselektivität aus. Vorteilhafterweise zeigen die erfin¬ dungsgemäßen und die erfindungsgemäß eingesetzten Katalysatoren zudem in der Regel eine hohe Regioselektivität. Weiterhin weisen die Katalysatoren im Allgemeinen eine hohe Stabilität unter den Hydroformylierungsbedingungen auf, so dass mit Ihnen in der Regel längere Katalysatorstandzeiten erzielt werden, als mit aus dem Stand der Technik bekannten Katalysatoren auf Basis herkömmlicher Chelatliganden. Vorteilhaft¬ erweise zeigen die erfindungsgemäßen und erfindungsgemäß eingesetzten Katalysa¬ toren weiterhin eine hohe Aktivität, so dass in der Regel die entsprechenden Aldehyde, bzw. Alkohole in guten Ausbeuten erhalten werden.The asymmetric hydroformylation according to the process of the invention is characterized by a high stereoselectivity. Advantageously, the catalysts according to the invention and the catalysts used according to the invention also generally have a high regioselectivity. Furthermore, the catalysts generally have a high stability under the hydroformylation conditions, so that with you usually longer catalyst life can be achieved than with the state of Technically known catalysts based on conventional chelating ligands. Advantageously, the catalysts according to the invention and those used according to the invention furthermore exhibit high activity, so that as a rule the corresponding aldehydes or alcohols are obtained in good yields.
Eine weitere wichtige 1-Hydro-2-Carbo-Addition ist die Umsetzung mit Cyanwas- serstoff, im Folgenden Hydrocyanierung genannt.Another important 1-Hydro-2-Carbo addition is the reaction with hydrogen cyanide, hereinafter called hydrocyanation.
Auch die zur Hydrocyanierung eingesetzten Katalysatoren umfassen Komplexe eines Metalls der VIII. Nebengruppe, insbesondere Cobalt, Nickel, Ruthenium, Rhodium, Palladium, Platin, bevorzugt Nickel, Palladium und Platin und ganz besonders bevor¬ zugt Nickel. Die Herstellung der Metallkomplexe kann, wie zuvor beschrieben erfolgen. Gleiches gilt für die in situ-Herstellung der erfindungsgemäßen Hydrocyanierungskata- lysatoren. Verfahren zur Hydrocyanierung sind in J. March, Advanced Organic Che- mistry, 4. Aufl., S. 811 - 812 beschrieben, worauf hier Bezug genommen wird.The catalysts used for the hydrocyanation include complexes of a metal of subgroup VIII, in particular cobalt, nickel, ruthenium, rhodium, palladium, platinum, preferably nickel, palladium and platinum and very particularly preferably nickel. The preparation of the metal complexes can be carried out as described above. The same applies to the in situ preparation of the hydrocyanation catalysts according to the invention. Methods for hydrocyanation are described in J. March, Advanced Organic Chemistry, 4th ed., Pp. 811-812, which is incorporated herein by reference.
Nach einer weiteren bevorzugten Ausführungsform handelt es sich bei der 1-Hydro-2- Carbo-Addition um eine Umsetzung mit Kohlenmonoxid und wenigstens einer Verbin¬ dung mit einer nucleophilen Gruppe, im Folgenden als Carbonylierung bezeichnet.In a further preferred embodiment, the 1-hydro-2-carboo addition is a reaction with carbon monoxide and at least one compound having a nucleophilic group, hereinafter referred to as carbonylation.
Auch die Carbonylierungskatalysatoren umfassen Komplexe eines Metalls der VIII. Nebengruppe, bevorzugt Nickel, Cobalt, Eisen, Ruthenium, Rhodium und Palladium, insbesondere Palladium. Die Herstellung der Metallkomplexe kann wie zuvor beschrie¬ ben erfolgen. Gleiches gilt für die in situ-Herstellung der erfindungsgemäßen Carbony- lierungskatalysatoren.The carbonylation catalysts also include complexes of a metal of subgroup VIII, preferably nickel, cobalt, iron, ruthenium, rhodium and palladium, in particular palladium. The preparation of the metal complexes can be carried out as described above. The same applies to the in situ preparation of the carbonylation catalysts according to the invention.
Vorzugsweise sind die Verbindungen mit einer nucleophilen Gruppe, ausgewählt unter Wasser, Alkoholen, Thiolen, Carbonsäureestern, primären und sekundären Aminen.Preferably, the compounds are having a nucleophilic group selected from water, alcohols, thiols, carboxylic acid esters, primary and secondary amines.
Eine bevorzugte Carbonylierungsreaktion ist die Überführung von Olefinen mit Koh¬ lenmonoxid und Wasser zu Carbonsäuren (Hydrocarboxylierung).A preferred carbonylation reaction is the conversion of olefins with carbon monoxide and water to carboxylic acids (hydrocarboxylation).
Die Carbonylierung kann in Gegenwart von Aktivierungsmitteln erfolgen. Geeignete Aktivierungsmittel sind z. B. Brönsted-Säuren, Lewis-Säuren, wie z. B. BF3, AICI3, ZnCI2, und Lewis-Basen.The carbonylation can be carried out in the presence of activating agents. Suitable activating agents are, for. B. Bronsted acids, Lewis acids, such as. B. BF 3 , AICI 3 , ZnCl 2 , and Lewis bases.
Eine weitere wichtige 1 ,2-Addition ist die Hydroacylierung. So gelangt man bei der asymmetrischen intramolekularen Hydroacylierung durch Umsetzung eines ungesättig¬ ten Aldehyds zu optisch aktiven cyclischen Ketonen. Bei der asymmetrischen intermo- lekularen Hydroacylierung gelangt man durch Umsetzung eines prochiralen Olefins mit einem Acylhalogenid in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Ketonen. Geeignete Verfahren zur Hydroacylierung sind in J. March, Ad¬ vanced Organic Chemistry, 4. Aufl., S. 811 beschrieben, worauf hier Bezug genommen wird.Another important 1,2-addition is hydroacylation. In asymmetric intramolecular hydroacylation, for example, reaction of an unsaturated aldehyde leads to optically active cyclic ketones. Asymmetric intermolecular hydroacylation is achieved by the reaction of a prochiral olefin an acyl halide in the presence of a chiral catalyst as described above to chiral ketones. Suitable processes for the hydroacylation are described in J. March, Advanced Organic Chemistry, 4th ed., P. 811, to which reference is made here.
Eine weitere wichtige 1 ,2-Addition ist die Hydroamidierung. So gelangt man durch Um¬ setzung einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit Kohlenmonoxid und Ammoniak, einem primären oder ei¬ nem sekundären Amin in Gegenwart eines chiralen Katalysators, wie zuvor beschrie- ben, zu chiralen Amiden.Another important 1,2-addition is hydroamidation. Thus, by reaction of a prochiral compound containing at least one ethylenically unsaturated double bond with carbon monoxide and ammonia, a primary or a secondary amine in the presence of a chiral catalyst, as described above, to give chiral amides.
Eine weitere wichtige 1 ,2-Addition ist die Hydroveresterung. So gelangt man durch Umsetzung einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit Kohlenmonoxid und einem Alkohol in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Estern.Another important 1,2-addition is hydroesterification. Thus, by reacting a prochiral compound containing at least one ethylenically unsaturated double bond with carbon monoxide and an alcohol in the presence of a chiral catalyst as described above, one obtains chiral esters.
Eine weitere wichtige 1 ,2-Addition ist die Hydroborierung. So gelangt man durch Um¬ setzung einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit Boran oder einer Boranquelle in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Trialkylboranen, die zu primären Al¬ koholen (z. B. mit NaOH/H2O2) oder zu Carbonsäuren oxidiert werden können. Geeig¬ nete Verfahren zur Hydroborierung sind in J. March, Advanced Organic Chemistry, 4. Aufl., S. 783 - 789 beschrieben, worauf hier Bezug genommen wird.Another important 1,2-addition is hydroboration. Thus, by reacting a prochiral compound which contains at least one ethylenically unsaturated double bond with borane or a borane source in the presence of a chiral catalyst, as described above, to give chiral trialkylboranes which are obtained as primary alcohols (for example with NaOH / H 2 O 2 ) or can be oxidized to carboxylic acids. Suitable processes for hydroboration are described in J. March, Advanced Organic Chemistry, 4th edition, pages 783-789, to which reference is made here.
Eine weitere wichtige 1 ,2-Addition ist die Hydrosilylierung. So gelangt man durch Um¬ setzung einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit einem Silan in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen mit Silylgruppen funktionalisierten Verbindungen. Aus prochiralen Olefinen resultieren chirale mit Silylgruppen funktionalisierte Alkane. Aus prochiralen Ketonen resultieren chirale Silylether oder -alkohole. Bei den Hydrosilylie- rungskatalysatoren ist das Übergangsmetall vorzugsweise ausgewählt unter Pt, Pd, Rh, Ru und Ir. Dabei kann es von Vorteil sein, Kombinationen oder Gemische eines der zuvor genannten Katalysatoren mit weiteren Katalysatoren einzusetzen. Zu den geeigneten zusätzlichen Katalysatoren zählt beispielsweise Platin in feinverteilter Form ("Platinmohr"), Platinchlorid und Platinkomplexe wie Hexachloroplatinsäure oder Divi- nyldisiloxan-Platin-Komplexe, z. B. Tetramethyldivinyldisiloxan-Platin-Komplexe. Ge¬ eignete Rhodiumkatalysatoren sind beispielsweise (RhCI(P(C6H5)S)3) und RhCI3. Ge¬ eignet sind weiterhin RuCI3 und IrCI3. Geeignete Katalysatoren sind weiterhin Lewis- Säuren wie AICI3 oder TiCI4 sowie Peroxide. Geeignete Silane sind z. B. halogenierte Silane, wie Trichlorsilan, Methyldichlorsilan, Dimethylchlorsilan und Trimethylsiloxydichlorsilan; Alkoxysilane, wie Trimethoxysilan, Triethoxysilan, Methyldimethoxysilan, Phenyldimethoxysilan, 1 ,3,3,5,5,7,7-Heptamethyl-i ,1-dimethoxytetrasiloxan sowie Acyloxysilane.Another important 1,2-addition is hydrosilylation. Thus, by reaction of a prochiral compound which contains at least one ethylenically unsaturated double bond with a silane in the presence of a chiral catalyst, as described above, chiral silyl-functionalized compounds are obtained. Prochiral olefins result in chiral silyl-functionalized alkanes. Prochiral ketones result in chiral silyl ethers or alcohols. In the hydrosilylation catalysts, the transition metal is preferably selected from Pt, Pd, Rh, Ru and Ir. It may be advantageous to use combinations or mixtures of one of the aforementioned catalysts with other catalysts. Examples of suitable additional catalysts include platinum in finely divided form ("platinum black"), platinum chloride and platinum complexes such as hexachloroplatinic acid or divinyldisiloxane-platinum complexes, eg. B. Tetramethyldivinyldisiloxan-platinum complexes. Suitable rhodium catalysts are, for example, (RhCl (P (C 6 H 5 ) S ) 3 ) and RhCl 3 . Also suitable are RuCl 3 and IrCl 3 . Suitable catalysts are also Lewis acids such as AICI 3 or TiCl 4 and peroxides. Suitable silanes are, for. Halogenated silanes such as trichlorosilane, methyldichlorosilane, dimethylchlorosilane and trimethylsiloxydichlorosilane; Alkoxysilanes such as trimethoxysilane, triethoxysilane, methyldimethoxysilane, phenyldimethoxysilane, 1, 3,3,5,5,7,7-heptamethyl-i, 1-dimethoxytetrasiloxane and acyloxysilanes.
Die Reaktionstemperatur bei der Silylierung liegt vorzugsweise in einem Bereich von 0 bis 140 0C, besonders bevorzugt 40 bis 120 0C. Die Reaktion wird üblicherweise unter Normaldruck durchgeführt, kann jedoch auch bei erhöhten Drücken, wie z. B. im Be¬ reich von etwa 1 ,5 bis 20 bar, oder verringerten Drücken, wie z. B. 200 bis 600 mbar, erfolgen.The reaction temperature in the silylation is preferably in a range of 0 to 140 0 C, more preferably 40 to 120 0 C. The reaction is usually carried out under atmospheric pressure, but can also at elevated pressures, such as. B. Be¬ range of about 1, 5 to 20 bar, or reduced pressures such. B. 200 to 600 mbar done.
Die Reaktion kann ohne Lösungsmittel oder in Gegenwart eines geeigneten Lösungs¬ mittels erfolgen. Als Lösungsmittel bevorzugt sind beispielsweise Toluol, Tetrahydrofu- ran und Chloroform.The reaction can be carried out without solvent or in the presence of a suitable solvent. Preferred solvents are, for example, toluene, tetrahydrofuran and chloroform.
Eine weitere wichtige 1 ,2-Addition ist die Aminolyse (Hydroaminierung). So gelangt man durch Umsetzung einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit Ammoniak, einem primären oder einem se¬ kundären Amin in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen primären, sekundären oder tertiären Aminen. Geeignete Verfahren zur Hydro¬ aminierung sind in J. March, Advanced Organic Chemistry, 4. Aufl., S. 768 - 770 be¬ schrieben, worauf hier Bezug genommen wird.Another important 1,2-addition is aminolysis (hydroamination). Thus, by reacting a prochiral compound containing at least one ethylenically unsaturated double bond with ammonia, a primary or a secondary amine in the presence of a chiral catalyst, as described above, to chiral primary, secondary or tertiary amines. Suitable processes for hydroamination are described in J. March, Advanced Organic Chemistry, 4th edition, pages 768-770, to which reference is hereby made.
Eine weitere wichtige 1,2-Addition ist die Alkoholyse (Hydro-Alkoxy-Addition). So ge- langt man durch Umsetzung einer prochiralen Verbindung, die wenigstens eine ethyle¬ nisch ungesättigte Doppelbindung enthält, mit Alkoholen in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Ethern. Geeignete Verfahren zur Al¬ koholyse sind in J. March, Advanced Organic Chemistry, 4. Aufl., S. 763 - 764 be¬ schrieben, worauf hier Bezug genommen wird.Another important 1,2-addition is alcoholysis (hydro-alkoxy-addition). Thus, by reacting a prochiral compound which contains at least one ethylenically unsaturated double bond with alcohols in the presence of a chiral catalyst, as described above, to give chiral ethers. Suitable methods for alcoholysis are described in J. March, Advanced Organic Chemistry, 4th ed., Pp. 763-764, to which reference is made here.
Eine weitere wichtige Reaktion ist die Isomerisierung. So gelangt man von einer prochi¬ ralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Verbin¬ dungen.Another important reaction is isomerization. Thus, from a prochi¬ ral compound containing at least one ethylenically unsaturated double bond, in the presence of a chiral catalyst, as described above, to chiral Verbin¬ tions.
Eine weitere wichtige Reaktion ist die Cyclopropanierung. So gelangt man von einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit einer Diazoverbindung in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Cyclopropanen. Eine weitere wichtige Reaktion ist die Metathese. So gelangt man von einer prochiralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit einem weiteren Olefin in Gegenwart eines chiralen Katalysators, wie zuvor beschrie¬ ben, zu chiralen Kohlenwasserstoffen.Another important reaction is cyclopropanation. Thus, a prochiral compound containing at least one ethylenically unsaturated double bond is reacted with a diazo compound in the presence of a chiral catalyst as described above to give chiral cyclopropanes. Another important reaction is metathesis. Thus, a prochiral compound containing at least one ethylenically unsaturated double bond with another olefin in the presence of a chiral catalyst, as described above, leads to chiral hydrocarbons.
Eine weitere wichtige Reaktion ist die Aldolkondensation. So gelangt man durch Um¬ setzung eines prochiralen Ketons oder Aldehyds mit einem Silylenolether in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Aldolen.Another important reaction is the aldol condensation. Thus, by reaction of a prochiral ketone or aldehyde with a silyl enol ether in the presence of a chiral catalyst, as described above, chiral aldols are obtained.
Eine weitere wichtige Reaktion ist die allylische Alkylierung. So gelangt man durch Umsetzung eines prochiralen Ketons oder Aldehyds mit einem allylischen Alkylie- rungsmittel in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chira¬ len Kohlenwasserstoffen.Another important reaction is allylic alkylation. Thus, by reacting a prochiral ketone or aldehyde with an allylic alkylating agent in the presence of a chiral catalyst, as described above, chiral hydrocarbons are obtained.
Eine weitere wichtige Reaktion ist die [4+2]-Cycloaddition. So gelangt man durch Um¬ setzung eines Diens mit einem Dienophil, wovon wenigstens eine Verbindung prochiral ist, in Gegenwart eines chiralen Katalysators, wie zuvor beschrieben, zu chiralen Cyc- lohexen-Verbindungen.Another important reaction is the [4 + 2] cycloaddition. Thus, by reacting a diene with a dienophile, at least one compound of which is prochiral, in the presence of a chiral catalyst, as described above, to give chiral cyclohexene compounds.
Ein weiterer Gegenstand der Erfindung ist die Verwendung von Katalysatoren, umfas¬ send wenigstens einen Komplex eines Metalls der VIII. Nebengruppe mit wenigstens einem Liganden, wie zuvor beschrieben, zur Hydroformylierung, Hydrocyanierung, Carbonylierung, Hydroacylierung, Hydroamidierung, Hydroveresterung, Hydrosilylie- rung, Hydroborierung, Hydrierung, Aminolyse, Alkoholyse, Isomerisierung, Metathese, Cyclopropanierung oder [4+2]-Cycloaddition.Another object of the invention is the use of catalysts comprising at least one complex of a metal of VIII. Subgroup with at least one ligand, as described above, for hydroformylation, hydrocyanation, carbonylation, hydroacylation, hydroamidation, hydroesterification, hydrosilylation, hydroboration , Hydrogenation, aminolysis, alcoholysis, isomerization, metathesis, cyclopropanation or [4 + 2] cycloaddition.
Das erfindungsgemäße Verfahren eignet sich zur Herstellung einer Vielzahl nützlicher optisch aktiver Verbindungen. Dabei wird stereoselektiv ein chirales Zentrum erzeugt. Beispielhafte optisch aktive Verbindungen, die sich nach dem erfindungsgemäßen Ver- fahren herstellen lassen sind substituierte und unsubstituierte Alkohole oder Phenole, Amine, Amide, Ester, Carbonsäuren oder Anhydride, Ketone, Olefine, Aldehyde, Nitrile und Kohlenwasserstoffe. Bevorzugt nach dem erfindungsgemäßen asymmetrischen Hydroformylierungsverfahren hergestellte optisch aktive Aldehyde umfassen beispiels¬ weise S-2-(p-isobutylphenyl)propionaldehyd, S-2-(6-methoxynaphthyl)propionaldehyd, S-2-(3-benzoylphenyl)propionaldehyd, S-2-(p-thienoylphenyl)propionaldehyd, S-2-(3-fluoro-4-phenyl)phenylpropionaldehyd, S-2-[4-(1 ,3-dihydro-l-oxo-2H-isoindol-2-yl)phenyl]propionaldehyd, S-2-(2-methylacetaldehyde)-5-ben∑oylthiophen, etc. Weitere nach dem erfindungsgemäßen Verfahren (einschließlich einer etwaigen Derivatisierung) herstellbare optisch aktive Verbindungen sind in Kirk-Othmer, Encyclopedia ofThe inventive method is suitable for the preparation of a variety of useful optically active compounds. This stereoselectively generates a chiral center. Exemplary optically active compounds which can be prepared by the process according to the invention are substituted and unsubstituted alcohols or phenols, amines, amides, esters, carboxylic acids or anhydrides, ketones, olefins, aldehydes, nitriles and hydrocarbons. Optically active aldehydes prepared by the asymmetric hydroformylation process according to the invention include, for example, S-2- (p-isobutylphenyl) propionaldehyde, S-2- (6-methoxynaphthyl) propionaldehyde, S-2- (3-benzoylphenyl) propionaldehyde, S-2 - (p-thienoylphenyl) propionaldehyde, S-2- (3-fluoro-4-phenyl) phenylpropionaldehyde, S-2- [4- (1,3-dihydro-1-oxo-2H-isoindol-2-yl) -phenyl propionaldehyde, S-2- (2-methylacetaldehyde) -5-benzoylthiophene, etc. Other optically active compounds which can be prepared by the process according to the invention (including any derivatization) are described in Kirk-Othmer, Encyclopedia of
Chemical Technology, Third Edition, 1984, und The Merck Index, An Encyclopedia of Edition, 1984, und The Merck Index, An Encyclopedia of Chemicals, Drugs and Biolo- gicals, Eleventh Edition, 1989, beschrieben, worauf hier Bezug genommen wird.Chemical Technology, Third Edition, 1984, and The Merck Index, An Encyclopedia of Edition, 1984, and The Merck Index, to Encyclopedia of Chemicals, Drugs and Biologicals, Eleventh Edition, 1989, which is incorporated herein by reference.
Das erfindungsgemäße Verfahren erlaubt die Herstellung von optisch aktiven Produk- ten mit hoher Enantioselektivität und erforderlichenfalls Regioselektivität, z. B. bei der Hydroformylierung. Enantiomere Überschüsse (ee) von mindestens 50 %, bevorzugt mindestens 60 % und insbesondere mindestens 70 % können erzielt werden.The inventive method allows the production of optically active products with high enantioselectivity and, if necessary, regioselectivity, for. B. in the hydroformylation. Enantiomeric excesses (ee) of at least 50%, preferably at least 60% and in particular at least 70% can be achieved.
Die Isolierung der erhaltenen Produkte gelingt nach üblichen, dem Fachmann bekann- ten Verfahren. Dazu zählen beispielsweise Lösungsmittelextraktion, Kristallisation, Destillation, Verdampfen z. B. in einem Wischblatt- oder Fallfilmverdampfer, etc.The isolation of the products obtained succeeds according to customary processes known to the person skilled in the art. These include, for example, solvent extraction, crystallization, distillation, evaporation z. In a wiper blade or falling film evaporator, etc.
Die nach dem erfindungsgemäßen Verfahren erhaltenen optisch aktiven Verbindungen können einer oder mehreren Folgeumsetzung(en) unterzogen werden. Derartige Ver- fahren sind dem Fachmann bekannt. Dazu zählen beispielsweise die Veresterung von Alkoholen, die Oxidation von Alkoholen zu Aldehyden, N-Alkylierung von Amiden, Addi¬ tion von Aldehyden an Amide, Nitrilreduktion, Acylierung von Ketonen mit Estern, Acy- lierung von Aminen, etc. Beispielsweise können durch erfindungsgemäße asymmetri¬ sche Hydroformylierung erhaltene optisch aktive Aldehyde einer Oxidation zu Carbon- säuren, Reduktion zu Alkoholen, Aldolkondensation zu α,ß-ungesättigten Verbindun¬ gen, reduktiven Aminierung zu Aminen, Aminierung zu Iminen, etc., unterzogen wer¬ den.The optically active compounds obtained by the process according to the invention may be subjected to one or more secondary reactions. Such methods are known to the person skilled in the art. These include, for example, the esterification of alcohols, the oxidation of alcohols to aldehydes, N-alkylation of amides, addition of aldehydes to amides, nitrile reduction, acylation of ketones with esters, acylation of amines, etc. For example, asymmetri ¬ hydroformylation obtained optically active aldehydes of an oxidation to carboxylic acids, reduction to alcohols, aldol condensation to α, ß-unsaturated Verbindun¬ gene, reductive amination to amines, amination to imines, etc., wer¬ subjected.
Eine bevorzugte Derivatisierung umfasst die Oxidation eines nach dem erfindungsge- mäßen asymmetrischen Hydroformylierungsverfahren hergestellten Aldehyds zur ent¬ sprechenden optisch aktiven Carbonsäure. So können eine Vielzahl pharmazeutisch wichtiger Verbindungen, wie S-Ibuprofen, S-Naproxen, S-Ketoprofen, S-Suprofen, S-Fluorbiprofen, S-Indoprofen, S-Tiaprofensäure etc. hergestellt werden.A preferred derivatization comprises the oxidation of an aldehyde prepared according to the asymmetric hydroformylation process according to the invention to give the corresponding optically active carboxylic acid. Thus, a variety of pharmaceutically important compounds, such as S-ibuprofen, S-naproxen, S-ketoprofen, S-suprofen, S-fluorobiprofen, S-indoprofen, S-tiaprofenoic acid, etc. can be prepared.
Einige bevorzugte Derivatisierungen werden in der folgenden Tabelle hinsichtlich Ole- finausgangsmaterial, Aldehydzwischenprodukt und Endprodukt aufgezählt: Some preferred derivatizations are listed in the following table for olefin starting material, aldehyde intermediate and end product:
-4-4
BeispieleExamples
Synthese der LigandenSynthesis of ligands
Beispiel 1 : BINASKATExample 1: BINASKAT
BINASKATBINASKAT
Es werden 150 ml THF in einem mit Schutzgas gespülten Kolben vorgelegt. Unter Rühren werden 14,5 g (110 mmol) PCI3 zugegeben. Eine Mischung aus 27,7 g 3-Methylindol (220 mmol) und 25,6 g NEt3 (250 mmol) in 30 ml THF werden bei 15 bis 20 0C langsam zugetropft. Anschließend wird der Tropftrichter noch zweimal mit 20 ml THF nachgespült. Die Reaktionslösung wird unter Rückfluss gerührt. Nach 4 h Reakti¬ onszeit zeigt die GC-Kontrolle 70 % Zielprodukt an. Das THF wird entfernt und der verbleibende Rückstand in 160 ml Toluol aufgenommen.150 ml of THF are placed in a flask purged with protective gas. With stirring, 14.5 g (110 mmol) of PCI 3 are added. A mixture of 27.7 g of 3-methylindole (220 mmol) and 25.6 g of NEt 3 (250 mmol) in 30 ml of THF are slowly added dropwise at 15 to 20 0 C. Subsequently, the dropping funnel is rinsed twice more with 20 ml of THF. The reaction solution is stirred under reflux. After a reaction time of 4 h, the GC control indicates 70% of the target product. The THF is removed and the remaining residue taken up in 160 ml of toluene.
15 ml dieser Lösung werden in 50 ml Toluol aufgenommen. Zu dieser Lösung werden 1 ,7 g NEt3 (16,5 mmol) zugegeben. Unter Rühren wird eine Lösung aus 3,0 g (6,6 mmol) R-Diphenylphosphino-2'-hydroxy-1 ,1 '-binaphthyl in 20 ml Toluol langsam bei Raumtemperatur zugetropft. Die Reaktionslösung wird über Nacht bei Raumtempe¬ ratur gerührt. Anschließend wird das Lösungsmittel im Vakuum entfernt und der verbleibende Rückstand säulenchromatographisch gereinigt. Man erhält 3,63 g (74 % der Theorie) eines farblosen kristallinen Pulvers.15 ml of this solution are taken up in 50 ml of toluene. To this solution is added 1.7 g of NEt 3 (16.5 mmol). With stirring, a solution of 3.0 g (6.6 mmol) of R-diphenylphosphino-2'-hydroxy-1, 1 '-binaphthyl in 20 ml of toluene is slowly added dropwise at room temperature. The reaction solution is stirred overnight at room temperature. Subsequently, the solvent is removed in vacuo and the remaining residue is purified by column chromatography. This gives 3.63 g (74% of theory) of a colorless crystalline powder.
31 P-NMR (145 MHz): δ = 103,1 , -12,3 ppm31 P-NMR (145 MHz): δ = 103.1, -12.3 ppm
Asymmetrische HydroformylierungenAsymmetric hydroformylations
Beispiel 2:Example 2:
Hydroformylierung von Styrol mit Rh/BINASKATHydroformylation of styrene with Rh / BINASKAT
18,8 mg Rh(CO)2acac und 216 mg BINASKAT werden in einem Autoklaven in 15,8 g Toluol gelöst und mit Synthesegas bei 9 bar Reaktionsdruck 16 h bei 50 0C gerührt. Nach Zugabe von 1 ,75 g Styrol wird 3 h bei 60 0C und 9 bar Synthesegas gerührt. Der Umsatz beträgt 98 %. Der gaschromatographisch bestimmte ee-Wert beträgt 60 %.18.8 mg of Rh (CO) 2 acac and 216 mg of BINASKAT are dissolved in 15.8 g of toluene in an autoclave and stirred with synthesis gas at 9 bar reaction pressure for 16 h at 50 ° C. After addition of 1.75 g of styrene is stirred for 3 h at 60 0 C and 9 bar synthesis gas. The turnover is 98%. The gas chromatographically determined ee value is 60%.
Beispiel 3: Hydroformylierung von Vinylacetat mit Rh/BINASKATExample 3: Hydroformylation of vinyl acetate with Rh / BINASKAT
18,9 mg Rh(CO)2acac und 200 mg BINASKAT werden in einem Autoklaven in 15,7 g Toluol gelöst und mit Synthesegas bei 9 bar Reaktionsdruck 4 h bei 50 0C gerührt. Nach Zugabe von 1 ,75 g Styrol wird 24 h bei 50 0C und 9 bar Synthesegas gerührt. Der Umsatz beträgt 93 %. Der gaschromatographisch bestimmte ee-Wert beträgt 66 %.18.9 mg of Rh (CO) 2 acac and 200 mg of BINASKAT are dissolved in 15.7 g of toluene in an autoclave and stirred with synthesis gas at 9 bar reaction pressure for 4 h at 50 ° C. After addition of 1.75 g of styrene is stirred for 24 h at 50 0 C and 9 bar synthesis gas. The turnover is 93%. The gas chromatographically determined ee value is 66%.
Beispiel 4:Example 4:
Darstellung von Ligand 2Representation of ligand 2
In einem 250 ml Vierhalskolben wurden 1 ,28 g 6-Methoxyindol (8,70 mmol) sowie 0,62 g Phosphortrichlorid (4,51 mmol) in 10 ml THF vorgelegt. Zu dieser Lösung tropfte man bei -78 0C über eine Stunde eine Lösung von 2,02 g (20,0 mmol) Triethylamin in 5 ml THF. Im Anschluss daran wurde das Kühlbad entfernt und die Reaktionsmischung über Nacht rühren gelassen, bevor bei Raumtemperatur eine Lösung von 2,03 g (4,47 mmol) (R)-(+)-2-Diphenylphosphino-2'-hydroxy-1,1 '-binaphthyl in 10 ml THF zu¬ getropft wurde. Man ließ erneut über Nacht rühren und filtrierte anschließend den Fest- stoffanteil der Reaktionsmischung ab. Die erhaltene Lösung wurde eingeengt und der Rückstand aus Ethanol umkristallisiert.1.28 g of 6-methoxyindole (8.70 mmol) and 0.62 g of phosphorus trichloride (4.51 mmol) in 10 ml of THF were placed in a 250 ml four-necked flask. To this solution was added dropwise at -78 0 C for one hour, a solution of 2.02 g (20.0 mmol) of triethylamine in 5 ml of THF. Following this, the cooling bath was removed and the reaction mixture allowed to stir overnight before at room temperature a solution of 2.03 g (4.47 mmol) of (R) - (+) - 2-diphenylphosphino-2'-hydroxy-1, 1 '-Binaphthyl in 10 ml of THF was added dropwise. The mixture was stirred again overnight and then the solids content of the reaction mixture was filtered off. The resulting solution was concentrated and the residue was recrystallized from ethanol.
Man erhielt 2,78 g (3,58 mmol; 80 %) des Liganden als blassgelber Feststoff. Auf analoge Weise wurden die folgenden Verbindungen hergestellt:This gave 2.78 g (3.58 mmol, 80%) of the ligand as a pale yellow solid. In an analogous manner, the following compounds were prepared:
Beispiel 5:Example 5:
Asymmetrische Hydroformylierung von Styrol unter Verwendung von Ligand 2Asymmetric hydroformylation of styrene using ligand 2
In einem drei Mal mit 5 bar Synthesegas (CCVH2 = 1 :1 ) gespülten 100 ml Autoklaven wurden 17,1 mg Rh(CO)2acac (66 μmol) und 207 mg Ligand 2 (267 μmol) in 18,7 g Toluol vorgelegt. Es wurde 90 Minuten bei einer Temperatur von 50 0C mit 9 bar Syn- thesegas (CO/H2 = 1 :1 ) beaufschlagt, bevor mittels einer Schleuse 2,0 g Styrol (19 mmol) eingebracht wurden. Nach Einstellen des Drucks auf 20 bar Synthesegas (CO/H2 = 1 :1) wurde 15 Stunden bei 50 0C hydroformyliert. Es resultierte eine 99%ige Umsetzung des Edukts zu den 2- und 3-Phenylpropanalen. Insgesamt entfielen auf 2-Phenylpropanal 77 % (iso-Selektivität: 78 %), der erzielte ee-Wert lag bei 62 %.In a 100 ml autoclave purged three times with 5 bar synthesis gas (CCVH 2 = 1: 1), 17.1 mg Rh (CO) 2 acac (66 μmol) and 207 mg ligand 2 (267 μmol) in 18.7 g toluene submitted. It was 90 minutes at a temperature of 50 0 C with 9 bar Syn- Thesegas (CO / H 2 = 1: 1) applied before 2.0 g of styrene (19 mmol) were introduced by means of a lock. After adjusting the pressure to 20 bar synthesis gas (CO / H 2 = 1: 1) was hydroformylated at 50 0 C for 15 hours. This resulted in a 99% conversion of the starting material to the 2- and 3-phenylpropanals. Overall, 2-phenylpropanal accounted for 77% (iso-selectivity: 78%) and the ee value reached 62%.
Umsatzanalytik (GC, Direkteinspritzung):Sales analysis (GC, direct injection):
Säule: Macherei Nagel OV-1 , 25 m x 0,32 mm xθ,5 μm; Detektor: FID; Temperaturpro¬ gramm: 50 0C 2 min, 5 °C/min bis 90 0C, 90 0C 5 min, 20 °C/min bis 300 0C; Retenti- onszeiten: Rτ Styrol = 10,8 min, Rτ 2-Phenylpropanal = 18,4 min, RT3-Phenylpropanal = 19,5 min.Column: Machinery nail OV-1, 25 mx 0.32 mm xθ, 5 microns; Detector: FID; Temperaturpro¬ program: 50 0 C 2 min, 5 ° C / min to 90 0 C, 90 0 C 5 min, 20 ° C / min to 300 0 C; Retention times: R τ styrene = 10.8 min, R τ 2-phenylpropanal = 18.4 min, R T 3-phenylpropanal = 19.5 min.
ee-Analytik (GC, Direkteinspritzung):ee analysis (GC, direct injection):
Säule: BGB-174S, 30 m x 0,25 mm x 0,25 μm; Detektor: FID; Temperaturprogramm: 70 0C 10 min, 20 °C/min bis 120 0C, 120 0C 7 min, 20 °C/min bis 180 0C; 180 0C 5 min; Retentionszeiten: (R)-Enantiomer: 12,1 min, (S) Enantiomer: 12,7 min.Column: BGB-174S, 30 mx 0.25 mm x 0.25 μm; Detector: FID; Temperature program: 70 0 C 10 min, 20 ° C / min to 120 0 C, 120 0 C 7 min, 20 ° C / min to 180 0 C; 180 ° C 5 min; Retention times: (R) -enantiomer: 12.1 min, (S) enantiomer: 12.7 min.
Beispiele 6 bis 10:Examples 6 to 10:
Die Ergebnisse zur asymmetrischen Hydroformylierung von Styrol mit den Liganden 3 bis 7 wurden in analoger Weise erhalten und sind tabellarisch dargestellt:The results for the asymmetric hydroformylation of styrene with ligands 3 to 7 were obtained in an analogous manner and are shown in tabular form:

Claims

Patentansprüche claims
1. Phosphorchelatverbindungen der allgemeinen Formel I1. Phosphor chelate compounds of the general formula I.
worinwherein
Ra und Rß unabhängig voneinander für 5- bis 7-gliedrige heterocyclische Grup- pen stehen, die über ein Ringstickstoffatom an das Phosphoratom gebun¬ den sind oder Rα und Rp gemeinsam mit dem Phosphoratom, an das sie gebunden sind, für einen 5- bis 7-gliedrigen Heterocyclus stehen, der zu¬ sätzlich ein gegebenenfalls substituiertes Stickstoffatom und ein weiteres unter Sauerstoff und gegebenenfalls substituiertem Stickstoff ausgewähltes Heteroatom aufweist, die beide direkt an das Phosphoratom gebunden sind,R a and R 8 independently of one another are 5- to 7-membered heterocyclic groups which are bonded to the phosphorus atom via a ring nitrogen atom or R α and R p together with the phosphorus atom to which they are attached form a 5 to 7-membered heterocycle which additionally has an optionally substituted nitrogen atom and another heteroatom selected from oxygen and optionally substituted nitrogen, both of which are bonded directly to the phosphorus atom,
Rγ und Rδ unabhängig voneinander für Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl oder Hetaryl stehen, wobei die Alkylreste 1 , 2, 3, 4 oder 5 Substituenten, ausgewählt unter Cycloalkyl, Heterocycloalkyl, Aryl, Hetaryl, Alkoxy, Cyclo- alkoxy, Heterocycloalkoxy, Aryloxy, Hetaryloxy, Hydroxy, Thiol, Polyalkyle- noxid, Polyalkylenimin, COOH, Carboxylat, SO3H, Sulfonat, NE1E2, NE1E2E3X", Halogen, Nitro, Acyl oder Cyano aufweisen können, worin E1, E2 und E3 jeweils gleiche oder verschiedene Reste, ausgewählt unter Was- serstoff, Alkyl, Cycloalkyl, oder Aryl bedeuten und X" für ein Anionäquiva- lent steht,R γ and R δ independently of one another are alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where the alkyl radicals have 1, 2, 3, 4 or 5 substituents selected from cycloalkyl, heterocycloalkyl, aryl, hetaryl, alkoxy, cycloalkoxy, heterocycloalkoxy , Aryloxy, hetaryloxy, hydroxy, thiol, polyalkyleneoxide, polyalkylenimine, COOH, carboxylate, SO 3 H, sulphonate, NE 1 E 2 , NE 1 E 2 E 3 X " , halogen, nitro, acyl or cyano, in which E 1 , E 2 and E 3 are each the same or different radicals selected from among hydrogen, alkyl, cycloalkyl or aryl and X "is an anion equivalent,
und wobei die Cycloalkyl-, Heterocycloalkyl-, Aryl- und Hetarylreste Rγ und Rδ 1 , 2, 3, 4 oder 5 Substituenten aufweisen können, die ausgewählt sind unter Alkyl und den zuvor für die Alkylreste RY und Rδ genannten Substi¬ tuenten, oderand wherein the cycloalkyl, heterocycloalkyl, aryl and hetaryl radicals R γ and R δ may have 1, 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents mentioned above for the alkyl radicals R Y and R δ tuents, or
X für O, S, SiRεRξ oder NRη steht, worin Rε, Rξ und Rη unabhängig voneinan¬ der für Wasserstoff, Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl oder Hetaryl stehen, und Y für eine chirale zweiwertige verbrückende Gruppe steht.X ξ is O, S, SiR ε R or NR η, where R ε, ξ R and R independently η voneinan¬ of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, and Y stands for a chiral divalent bridging group.
2. Verbindungen nach Anspruch 1 , worin Rα und Rß unabhängig voneinander aus¬ gewählt sind unter Gruppen der Formeln II. a bis II. k2. Compounds according to claim 1, in which R α and R β are chosen independently from among groups of the formulas II. A to II. K
Alkauk
COOAIk COOAIk
(ILa) (H.b)(ILa) (H.b)
AIkOO OOAIkAIKOO OOAIk
(H-C) (ILd)(H-C) (ILd)
(ILe) (ILf) (H-Q)(ILe) (ILf) (H-Q)
(ILh) (ILi) (ILk) worin(ILh) (ILi) (ILk) wherein
Alk eine CrC4-Alkylgruppe ist undAlk is a C r C 4 alkyl group and
Ra, Rb, Rc und Rd unabhängig voneinander für Wasserstoff, C1-C4-AIKyI,R a , R b , R c and R d independently of one another represent hydrogen, C 1 -C 4 -alkyl,
C1-C4-AIkOXy, Acyl, Halogen, Trifluormethyl, CrC4-Alkoxycarbonyl oderC 1 -C 4 -alkoxy, acyl, halogen, trifluoromethyl, C r C 4 alkoxycarbonyl or
Carboxyl stehen.Carboxyl stand.
3. Verbindungen nach Anspruch 1 , worin Rα und Rß gemeinsam für einen 5- bis 7- gliedrigen Heterocyclus stehen, der gegebenenfalls zusätzlich ein-, zwei-, drei- oder vierfach mit Cycloalkyl, Heterocycloalkyl, Aryl oder Hetaryl anelliert ist, wo¬ bei der Heterocyclus und, falls vorhanden, die anellierten Gruppen unabhängig voneinander je einen, zwei, drei oder vier Substituenten tragen können, die aus- gewählt sind unter Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl, Hetaryl, Hydroxy,3. Compounds according to claim 1, wherein R α and R β together represent a 5- to 7-membered heterocycle which is optionally additionally fused once, twice, three or four times with cycloalkyl, heterocycloalkyl, aryl or hetaryl, where ¬ in which the heterocycle and, if present, the fused groups can each independently bear one, two, three or four substituents which are selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, hydroxy,
Thiol, Polyalkylenoxid, Polyalkylenimin, Alkoxy, Halogen, COOH, Carboxylat, SO3H, Sulfonat, NE4E5, NE4E5E6X", Nitro, Alkoxycarbonyl, Acyl und Cyano, worin E4, E5 und E6 jeweils gleiche oder verschiedene Reste, ausgewählt unter Was¬ serstoff, Alkyl, Cycloalkyl und Aryl bedeuten und X' für ein Anionäquivalent steht.Thiol, polyalkylene oxide, polyalkyleneimine, alkoxy, halogen, COOH, carboxylate, SO 3 H, sulfonate, NE 4 E 5 , NE 4 E 5 E 6 X " , nitro, alkoxycarbonyl, acyl and cyano, wherein E 4 , E 5 and E 6 each represent identical or different radicals selected from hydrogen, alkyl, cycloalkyl and aryl and X 'is an anion equivalent.
4. Verbindungen nach Anspruch 3, worin Rα und Rp gemeinsam mit dem Phosphor¬ atom, an das sie gebunden sind, für einen chiralen Heterocyclus stehen.4. Compounds according to claim 3, wherein R α and R p together with the Phosphor¬ atom to which they are attached, represent a chiral heterocycle.
5. Verbindungen nach Anspruch 3, worin Rα und Rp gemeinsam mit dem Phosphor- atorn, an das sie gebunden sind, für eine Gruppe der Formeln 11.1 bis II.35. Compounds according to claim 3, wherein R α and R p together with the phosphorus atom to which they are bonded, for a group of the formulas 11.1 to II.3
(11.1 ) (II.2) (11.1) (II.2)
(II.3)(II.3)
stehen, worinstand in which
R6 und R7 unabhängig voneinander für Wasserstoff, Alkyl, Cycloalkyl, Aryl, Het- aryl, Mesylat, Tosylat oder Trifluormethansulfonat stehen,R 6 and R 7 independently of one another represent hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, mesylate, tosylate or trifluoromethanesulfonate,
R 8 D9 D10 r>11 D12 D13 Π21 D22 D23 D24 D25 , K , K , K , K , K , , K , K , IΛ ,R 8 D 9 D 10 r> 11 D 12 D13 Π21 D 22 D 23 D 24 D 25, K, K, K, K, K, , K, K, IΛ,
R26 und R27 unabhängig voneinander für Wasserstoff, Alkyl, Cycloalkyl, He- terocycloalkyl, Aryl, Hetaryl, W'COORf, WCOO-M+, W'(SO3)Rf, W'(SO3)-M+,R 26 and R 27 are each independently hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, W'COOR f , WCOO-M + , W '(SO 3 ) R f , W' (SO 3 ) -M + .
W'PO3(Rf)(Rs), W(PO3)2XM+)S, WNE13E14, W(NE13E14E15J+X", W0Rf, WSRf, (CHR9CH2O)xRf, (CH2NE13)xRf, (CH2CH2NE13)xRf, Halogen, Triflu- ormethyl, Nitro, Acyl oder Cyano stehen,W'PO 3 (R f ) (R s ), W (PO 3 ) 2 XM + ) S , WNE 13 E 14 , W (NE 13 E 14 E 15 J + X " , W0R f , WSR f , (CHR 9 CH 2 O) x R f , (CH 2 NE 13 ) x R f , (CH 2 CH 2 NE 13 ) x R f , halogen, trifluoromethyl, nitro, acyl or cyano,
worinwherein
W für eine Einfachbindung, ein Heteroatom, eine Heteroatom-haltige Gruppe oder eine zweiwertige verbrückende Gruppe mit 1 bis 20 Brückenatomen steht,W represents a single bond, a heteroatom, a heteroatom-containing group or a divalent bridging group having 1 to 20 bridge atoms,
Rf, E13, E14, E15 jeweils gleiche oder verschiedene Reste, ausgewählt unterR f , E 13 , E 14 , E 15 are each the same or different radicals selected from
Wasserstoff, Alkyl, Cycloalkyl oder Aryl bedeuten,Hydrogen, alkyl, cycloalkyl or aryl,
R9 für Wasserstoff, Methyl oder Ethyl steht,R 9 is hydrogen, methyl or ethyl,
M+ für ein Kationäquivalent steht,M + is a cation equivalent,
X' für ein Anionäquivalent steht undX 'represents an anion equivalent and
x für eine ganze Zahl von 1 bis 240 steht, wobei jeweils zwei benachbarte Reste R8 bis R27 zusammen mit den Kohlen¬ stoffatomen des Rings, an die sie gebunden sind, auch für ein kondensiertes Ringsystem mit 1 , 2 oder 3 weiteren Ringen stehen können.x is an integer from 1 to 240, wherein in each case two adjacent radicals R 8 to R 27 together with the carbon atoms of the ring to which they are bonded may also stand for a fused ring system having 1, 2 or 3 further rings.
6. Verbindungen nach einem der vorhergehenden Ansprüche, wobei in der Formel die verbrückende Gruppe Y ausgewählt ist unter Gruppen der Formeln III. a und III. b6. Compounds according to one of the preceding claims, wherein in the formula, the bridging group Y is selected from groups of the formulas III. a and III. b
(HLa)(HLA)
RlV RV RVIII RIXRVV RV RVIII RIX
(iιι.b)(Iιι.b)
worinwherein
R', R'', R", R"', R'", R'"', Rιv, Rιv, Rv, Rvι, Rv", Rvl", Rlx, Rx, Rxι und RXI1 unabhängig voneinander für Wasserstoff, Alkyl, Cycloalkyl, Heterocycloalkyl, Aryl, Het- aryl, Hydroxy, Thiol, Polyalkylenoxid, Polyalkylenimin, Alkoxy, Halogen, SO3H, Sulfonat, NE10E11, Alkylen-NE10E11, Trifluormethyl, Nitro, Alkoxycar- bonyl, Carboxyl, Acyl oder Cyano stehen, worin E10 und E11 jeweils gleiche oder verschiedene Reste, ausgewählt unter Wasserstoff, Alkyl, Cycloalkyl und Aryl bedeuten. R ', R'', R ", R"', R ", R '"', R IV, R IV, R V, R VI, R v ", R vl", R lx, R x, R xι and R XI1 independently of one another are hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, het-aryl, hydroxy, thiol, polyalkylene oxide, polyalkyleneimine, alkoxy, halogen, SO 3 H, sulfonate, NE 10 E 11 , alkylene-NE 10 E 11 , Trifluoromethyl, nitro, alkoxycarbonyl, carboxyl, acyl or cyano, wherein E 10 and E 11 each represent identical or different radicals selected from hydrogen, alkyl, cycloalkyl and aryl.
7. Katalysator, umfassend wenigstens einen Komplex mit einem Übergangsmetall der als Liganden wenigstens eine Verbindung der Formel I1 wie in einem der An¬ sprüche 1 bis 6 definiert, enthält.7. Catalyst comprising at least one complex with a transition metal which as ligands at least one compound of formula I 1 as defined in any one of An¬ claims 1 to 6 contains.
8. Katalysator nach Anspruch 7, wobei das Metall ausgewählt ist unter Ruthenium, Rhodium, Iridium, Palladium und Platin.A catalyst according to claim 7, wherein the metal is selected from ruthenium, rhodium, iridium, palladium and platinum.
9. Verfahren zur Herstellung chiraler Verbindungen durch Umsetzung einer prochi- ralen Verbindung, die wenigstens eine ethylenisch ungesättigte Doppelbindung enthält, mit einem Substrat in Gegenwart eines chiralen Katalysators, wie in ei¬ nem der Ansprüche 7 oder 8 definiert.9. A process for the preparation of chiral compounds by reacting a prochiral compound containing at least one ethylenically unsaturated double bond, with a substrate in the presence of a chiral catalyst, as defined in ei¬ nem of claims 7 or 8 defined.
10. Verfahren nach Anspruch 9, wobei die prochirale Verbindung ausgewählt ist un¬ ter Olefinen, Aldehyden, Ketonen und Iminen.10. The process according to claim 9, wherein the prochiral compound is selected from olefins, aldehydes, ketones and imines.
11. Verfahren nach einem der Ansprüche 9 oder 10, bei dem es sich um eine Hydrie¬ rung, Hydroformylierung, Hydrocyanierung, Carbonylierung, Hydroacylierung, Hydroamidierung, Hydroveresterung, Hydrosilylierung, Hydroborierung, Aminolyse, Alkoholyse, Isomerisierung, Metathese, Cyclopropanierung, Aldol- kondensation, allylische Alkylierung oder [4+2]-Cycloaddition handelt.11. The method according to any one of claims 9 or 10, which is a hydrogenation tion, hydroformylation, hydrocyanation, carbonylation, hydroacylation, hydroamidation, hydroesterification, hydrosilylation, hydroboration, aminolysis, alcoholysis, isomerization, metathesis, cyclopropanation, aldol condensation allylic alkylation or [4 + 2] cycloaddition.
12. Verfahren nach einem der Ansprüche 9 bis 11 , bei dem es sich um eine 1 ,2-Addition, bevorzugt eine 1-Hydro-2-Carbo-Addition, handelt.12. The method according to any one of claims 9 to 11, which is a 1, 2-addition, preferably a 1-hydro-2-carbo-addition, is.
13. Verfahren nach einem der Ansprüche 9 bis 12, bei dem es sich um eine Hydro¬ formylierung handelt.13. The method according to any one of claims 9 to 12, wherein it is a hydroformylation.
14. Verfahren nach einem der Ansprüche 9 bis 11 , bei dem es sich um eine Hydrie¬ rung handelt.14. The method according to any one of claims 9 to 11, wherein it is a hydrogenation tion.
15. Verwendung eines Katalysators nach einem der Ansprüche 7 oder 8, zur Hydrie¬ rung, Hydroformylierung, Hydrocyanierung, Carbonylierung, Hydroacylierung, Hydroamidierung, Hydroveresterung, Hydrosilylierung, Hydroborierung, Aminoly¬ se, Alkoholyse, Isomerisierung, Metathese, Cyclopropanierung, Aldolkondensati- on, allylische Alkylierung oder [4+2]-Cycloaddition. 15. Use of a catalyst according to one of claims 7 or 8, for hydrogenation, hydroformylation, hydrocyanation, carbonylation, hydroacylation, hydroamidation, hydroesterification, hydrosilylation, hydroboration, aminolysis, alcoholysis, isomerization, metathesis, cyclopropanation, aldol condensation, allylic alkylation or [4 + 2] cycloaddition.
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