EP1628985A2 - Chiral ligands and their transition metal complexes - Google Patents

Chiral ligands and their transition metal complexes

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Publication number
EP1628985A2
EP1628985A2 EP04733263A EP04733263A EP1628985A2 EP 1628985 A2 EP1628985 A2 EP 1628985A2 EP 04733263 A EP04733263 A EP 04733263A EP 04733263 A EP04733263 A EP 04733263A EP 1628985 A2 EP1628985 A2 EP 1628985A2
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EP
European Patent Office
Prior art keywords
hept
trimethylbicyclo
pyridine
compounds
transition metal
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
EP04733263A
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German (de)
French (fr)
Inventor
Ulrich Scholz
Björn SCHLUMMER
Paul Knochel
Tanasri Bunlaksananusorn
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Saltigo GmbH
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Lanxess Deutschland GmbH
Saltigo GmbH
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Publication of EP1628985A2 publication Critical patent/EP1628985A2/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/24—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
    • C07F15/0033—Iridium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
    • C07F15/0033—Iridium compounds
    • C07F15/004—Iridium compounds without a metal-carbon linkage
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • 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
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • 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
    • C07F9/576—Six-membered rings
    • C07F9/60—Quinoline or hydrogenated quinoline ring systems

Definitions

  • the present invention relates to chiral nitrogen-phosphorus compounds and their transition metal complexes and the use of these transition metal complexes, in particular in asymmetric syntheses.
  • Enantiomerically enriched chiral compounds are valuable starting substances for the production of agrochemicals and pharmaceuticals.
  • Asymmetric catalysis has been used for the synthesis of such enantiomerically enriched chirals
  • R 1 and R 2 each independently represent an optionally substituted hydrocarbon radical with a total of 1 to 18 carbon atoms
  • a * stands for a carbodivalent, cyclic and optionally substituted radical with a total of 5 to 18 carbon atoms, which as such
  • Symmetry element has no mirror plane.
  • Alkyl or alkylene or alkoxy each independently means a straight-chain, cyclic, branched or unbranched alkyl- or alkylene or alkoxy radical. The same applies to the non-aromatic part of an arylalkyl radical.
  • C 1 -C 4 -alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl, C 1 -C 8 -alkyl furthermore, for example, n-pentyl,
  • -C-C 8 alkoxy is, for example, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy and tert-butoxy, n-pentoxy, neo-pentoxy, cyclo-hexoxy, cyclo-pentoxy , n-hexoxy and n-octoxy, CrC 12 alkoxy furthermore for example for adamantoxy, the isomeric menthoxy radicals, n-decoxy and n-dodecoxy.
  • C 2 -C 20 alkenyl is, for example, vinyl, 1-propenyl, isopropenyl, 1-butenyl, 1-hexenyl, 1-heptenyl, 1-octenyl or 2-octenyl.
  • Fluoroalkyl each independently means a straight-chain, cyclic, branched or unbranched alkyl radical which is substituted once, several times or completely by fluorine atoms.
  • C 1 -C 2 o-fluoroalkyl represents trifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, nonafluorobutyl, perfluorooctyl, perfluorododecyl and perfluorohexadecyl.
  • Aryl stands for a heteroaromatic radical with 5 to 18 carbon atoms in which none, one, two or three carbon atoms per cycle, in total
  • Molecule at least one carbon atom can be substituted by heteroatoms selected from the group nitrogen, sulfur or oxygen, however, preferably for a carbocyclic aromatic radical having 6 to 18 skeletal carbon atoms.
  • carbocyclic aromatic radicals with 6 to 18 carbon atoms are, for example, phenyl, naphthyl, phenanthrenyl, anthracenyl or fluorenyl, heteroaromatic radicals with 5 to 18 carbon atoms in which none, one, two or three carbon atoms per cycle, but at least one carbon atom in the entire molecule , Heteroatoms, selected from the group nitrogen, sulfur or oxygen, may be substituted, for example pyridinyl, oxazolyl, benzofuranyl, dibenzoftrranyl or quinolinyl.
  • COO (CC 8 alkyl), CON (-C 8 alkyl) 2 , COO -Cs arylalkyl), COO (C 4 -C 14 aryl), CO CrCs alkyl), C 5 -C 5 arylalkyl or Tri CrCe-alkyrjsiloxyl.
  • Azoaryl represents a heteroaromatic radical with 5 to 18 carbon atoms in which none, one, two or three carbon atoms per cycle, but at least one carbon atom in the entire molecule, but at least one carbon atom, can be substituted by heteroatoms, at least one nitrogen atom and optionally further heteroatoms are selected from the group nitrogen,
  • Arylalkyl each independently means a straight-chain, cyclic, branched or unbranched alkyl radical which can be replaced simply, repeatedly or completely by aryl
  • C 5 -C 1 arylalkyl is, for example, benzyl, 1-phenylethyl, 1-phenylpropyl, 2-phenylpropyl and 1-naphthylmethyl, and optionally the isomeric or stereoisomeric forms.
  • Arylalkenyl each independently means a straight-chain, cyclic, branched or unbranched alkenyl radical which can be substituted once, several times or completely by aryl radicals as defined above.
  • C 6 -C 1 arylalkenyl represents, for example, 1-phenylvinyl or 2-phenylvinyl.
  • a * is a carbodivalent and cyclic radical
  • the conformative mobility of the ethylene bridge carrying the Het and PR R 2 radicals is usually severely restricted.
  • the residues Het and PR R are preferably arranged transposed to one another.
  • Stereomerically enriched compounds of the formula (I) are preferred. Enriched with stereomers in the sense of the invention means that one stereomer is present in a larger relative proportion than the respective other stereomers.
  • the other stereoisomers can be both enantiomers and diastereomers.
  • the relative amount of substance of only one stereoisomer, based on the sum of all stereoisomers, is preferably at least 90%, particularly preferably at least 95% and very particularly preferably at least 98.5%.
  • R and R are preferably each independently of the other: C 1 -C 2 -alkyl,
  • R 1 and R 2 ' are particularly preferably each identical: C 3 -C 12 -alkyl, C -C 14 -
  • R and R> 2 very particularly preferably each represent: iso-propyl, tert-butyl, cyclohexyl, phenyl, 2- (C 1 -C 8 ) alkylphenyl such as o-tolyl, 3- (C 1 -C 8 ) -alkylphenyl such as m-tolyl, 4- (C 1 -C 8 ) -alkylphenyl such as p-tolyl, 2,6-di- (C 1 -C 8 ) -alkylphenyl such as 2,6-
  • C 8 ) -alkoxyphenyl such as 2,6-dimethoxyphenyl, 3,5-di- (-C-C 8 ) alkoxyphenyl such as 3,5-di ethoxyphenyl, 3,4,5-tri- (C -C 8 ) alkoxyphenyl such as 3,4,5-trimethoxyphenyl, 3,5-dialkyl-4- (C 1 -C 8 ) alkoxyphenyl such as 3,5-dimethyl-4-anisyl, 3,5- (C 1 -C 8 ) dialkyl -4- di- (CrC 8 ) -alkylaminophenyl, 3,5-dimethyl-4-dimethylamino-phenyl, 4-di- (Ci-C 8 ) -alkylaminophenyl such as 4-diethylaminophenyl and 4-dimethylaminophenyl, 3,5-bis -
  • [(C 1 -C 4 ) -fluoroalkyl] phenyl such as 3,5-bis-trifluoromethyl-phenyl, 2,4-bis - [(-C-C 4 ) -fluoro-alkyl] phenyl such as 2,4-bis-trifluoromethyl-phenyl, 4 - [(C 1 -C 4 ) -fluoroalkyl] phenyl such as 4-trifluoromethylphenyl and phenyl substituted by one, two, three, four or five times by fluorine and / or chlorine, fluorenyl or naphthyl such as 4-fluorophenyl and 4-chlorine - phenyl and furanyl.
  • Azoaryl is preferably 2-pyridyl or 2-quinolyl, it being possible for the radicals mentioned to be further substituted by one, two or three radicals which are each independently selected from the group chlorine, bromine, fluorine, C 1 -C 12 -alkyl, C 4 -C ⁇ o-AryL C 5 -C n arylalkyl and CC 12 alkoxy.
  • Azoaryl very particularly preferably represents 2-pyridyl, 6-bromo-2-pyridyl, 6-phenyl-2-pyridyl and 2-quinolyl.
  • Particularly preferred compounds of the formula (I) are those of the formulas (Ia) and (1b)
  • R, R and Het have the meanings and preferred ranges given above.
  • the compounds of the formula (I) or (la) and (Ib) can be prepared, for example, starting from compounds of the formula (II) according to the scheme below.
  • X 1 and X 2 each independently represent chlorine, bromine, iodine or a sulfonate, preferably bromine, iodine or a C 1 -C -perfluoroalkyl sulfonate.
  • the metalation can be carried out, for example, in such a way that the compounds of the formula (DI) are converted in a manner known per se into an analogous organozinc or organomagnesium compound and this is then reacted with compounds of the formula (H) in the presence of a catalyst to give compounds of the formula ( IN) are implemented.
  • Palladium or nickel complexes for example, can be used as the catalyst in step a).
  • Preferred compounds of the formula (IN) are those of the formulas (INa) and (INb):
  • Step b) can be carried out in such a way that Neritatien of formula (N) in the presence of a base, which can at least partially deprotonate the Neritatien of formula (N) in the presence of a solvent to compounds of formula (I).
  • Preferred bases are alcoholates, preferred solvents sulfoxides such as dimethyl sulfoxide, sulfones such as tetramethylene sulfone or secondary carboxamides such as dimethylformamide or ⁇ -methylpyrrolidone.
  • step b) the compounds of the formula (IN) can be reacted according to the following scheme in a step c) by reaction with Neritatien of the formula (NT) to Neritatien of the formula (NU) and in a step d) the Neritatien of the formula ( VIT) to reduce compounds of formula (I).
  • Step c) can be carried out completely analogously to step b), step d) in a manner known per se, for example by reduction with silanes such as in particular trichlorosilane in the presence of a base such as in particular triethylamine.
  • the method comprising steps c) and d) can be of advantage in particular when using electron-rich phosphines of the formula (IJT).
  • Preferred compounds of the formula (VIT) are those of the formulas (VIIa) and
  • the invention furthermore comprises transition metal complexes which contain the compound of the formula (I) according to the invention. Transition metal complexes which contain stereoisomerically enriched Neritatien of formula (I) are preferred.
  • Transition metal complexes are preferably complexes of ruthenium, osmium,
  • Cobalt rhodium, iridium, nickel, palladium, platinum and copper, particularly preferably complexes of ruthenium, rhodium, iridium, nickel and palladium and particularly preferably complexes of palladium and iridium.
  • transition metal complexes according to the invention are particularly suitable as
  • the invention therefore also includes catalysts which contain the transition metal complexes according to the invention.
  • Isolated transition metal complexes which contain the Neritatien of formula (I) are preferably those in which the ratio of transition metal to compound of formula (I) is 1: 1.
  • L 1 in each case represents a C 2 -C 12 alkene such as, for example, ethylene or cyclooctene or a nitrile such as, for example, acetonitrile, benzonitrile or benzyl nitrile, or
  • L ] 2 together represents a (C 4 -C 2 ) -diene such as, for example, bicyclo [2.1.1] hepta-2,5-diene ( ⁇ orbornadiene) or 1,5-cyclooctadiene and
  • a non or weakly coordinating anion such as methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate,
  • transition metal complexes are those which can be obtained by reacting transition metal compounds and compounds of the formula (I).
  • Suitable transition metal compounds are, for example, those of the formula
  • q stands for rhodium, iridium and ruthenium for 3, for nickel, palladium and platinum for 2 and for copper for 1,
  • L 1 each represents a C 2 -C 12 alkene such as, for example, ethylene or cyclooctene or a nitrile such as, for example, acetonitrile, benzonitrile or benzyl nitrile, or
  • L 2 together represents a (C 4 -C 12 ) diene such as, for example, bicyclo [2.1.1] hepta-2,5-diene (norbornadiene) or 1,5-cyclooctadiene
  • L 2 represents aryl radicals such as, for example, cymol, mesityl, phenyl or cyclooctadiene, norbornadiene or methylallyl
  • L 3 stands for (C 4 -C 12 ) diene such as, for example, bicyclo [2.1.1] hepta-2,5-diene (norbornadiene) or 1,5-cyclooctadiene and
  • An 4 for a non or weakly coordinating anion such as methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate, Perchlorate, hexafluoroantimonate, tetra (bis-3,5-trifluromethylphenyl) borate or tetraphenyl borate.
  • transition metal compounds are, for example, Ni (1,5-cyclo-octadiene) 2 , Pd 2 (dibenzylidene acetone) 3 , Pd [PPh 3 ], cyclopentadienyl 2 Ru,
  • Metal content for example 25 to 200 mol% based on the one used
  • Compound of the formula (I) are preferably 50 to 150 mol%, very particularly preferably 75 to 125 mol% and even more preferably 100 to 115 mol%.
  • the catalysts which contain the transition metal complexes according to the invention are particularly suitable for 1,4-additions, allylic substitutions, hydroboration, hydroformylation, hydrocyanation, Heck reactions and hydrogenation.
  • the catalysts contain transition metal complexes which contain stereoisomerically enriched compounds of the formula (I), the catalysts are particularly suitable for carrying out the above-mentioned reactions asymmetrically.
  • bonds such as prochiral imines.
  • the invention therefore also encompasses a process for the preparation of stereoisomerically enriched, preferably enantiomerically enriched compounds, which is characterized in that the compounds which are stereoisomerically enriched, preferably enantiomerically enriched, either by catalytic hydrogenation of olefms, enamines, enamides, imines or ketones or by
  • Hydroboration of alkenes and, if appropriate, subsequent oxidation or are obtained by allylic substitution and the catalysts used are those which contain transition metal complexes of stereoisomerically enriched compounds of the formula (I) with the meaning given there.
  • the transition metal complex can be, for example, 0.001 to 5 mol%, based on the metal content, based on the substrate used, preferably 0.001 to 0.5 mol%, very particularly preferably 0.001 to 0.1 mol%.
  • asymmetric hydrogenation, asymmetric hydroboration can be carried out, for example, in such a way that the catalyst is optionally produced from a transition metal compound and a stereoisomerically enriched compound of the formula (I) in a suitable solvent, the substrate is added and the reaction mixture is placed under hydrogen pressure at the reaction temperature become or a suitable one
  • asymmetric allylic substitutions can be carried out, for example, in such a way that the catalyst consists of a transition metal compound and a stereoisomerically enriched compound of
  • Formula (I) is optionally generated in a suitable solvent and the substrate and the nucleophile are added.
  • catalysts are preferably used which contain iridium compounds of the formula (I) and for allylic ones
  • Substitutions are preferably used catalysts which contain palladium complexes of compounds of formula (I).
  • the catalysts of the invention are particularly suitable in a process for the preparation of stereoisomerically enriched, preferably enantiomerically enriched, active ingredients of medicaments and agricultural chemicals, or intermediates of these two classes.
  • the advantage of the present invention is that the ligands can be produced in an efficient manner and their electronic and steric properties are variable over a wide range starting from readily available starting materials.
  • 'Furthermore, according to the invention show ligands and their transition metal complexes, especially in asymmetric hydrogenations, allylic substitutions hydroboration and good enantioselectivity and conversion rates.
  • Example 3 Analogously to Example 3, the product mentioned above was started from 2,6-disbromopyridine in a yield of 70% of theory. Th. Received.
  • Example 3 Analogously to Example 3, the product mentioned above was started from 2-bromopyridine and the vinyl triflate from Example 2 in a yield of 85% of theory. Th. Received.
  • Example 10 Analogously to Example 10, the product mentioned above was started with the compound from Example 6 with diphenylphosphine oxide in a yield of 86% of theory. Th. Received.
  • Example 10 Analogously to Example 10, the product mentioned above was started with the compound from Example 9 with diphenylphosphine oxide in a yield of 78% of theory. Th. Received.

Abstract

The invention relates to chiral phosphorus compounds and their transition metal complexes, in addition to the use of said transition metal complexes, in particular in asymmetric syntheses.

Description

Chirale Liganden und deren UbergangsmetallkomplexeChiral ligands and their transition metal complexes
Die vorliegende Erfindung betrifft chirale Stickstoff-Phosphorverbindungen und deren Ubergangsmetallkomplexe sowie die Verwendung dieser Ubergangsmetallkomplexe insbesondere in asymmetrischen Synthesen.The present invention relates to chiral nitrogen-phosphorus compounds and their transition metal complexes and the use of these transition metal complexes, in particular in asymmetric syntheses.
Enantiomerenangereicherte chirale Verbindungen sind wertvolle Ausgangssubstanzen zur Herstellung von Agrochemikalien und Pharmazeutika. Dabei hat die asym- metrische Katalyse für die Synthese solcher enantiomerenangereicherten chiralenEnantiomerically enriched chiral compounds are valuable starting substances for the production of agrochemicals and pharmaceuticals. Asymmetric catalysis has been used for the synthesis of such enantiomerically enriched chirals
Verbindungen eine große technische Bedeutung gewonnen.Connections gained great technical importance.
Die Vielzahl der Publikationen auf dem Gebiet der asymmetrischen Synthese zeigen deutlich, dass Ubergangsmetallkomplexe von Stickstoff-Phosphorverbindungen als Katalysatoren in asymmetrisch geführten Reaktionen wie insbesondere allyhschenThe large number of publications in the field of asymmetric synthesis clearly show that transition metal complexes of nitrogen-phosphorus compounds as catalysts in asymmetrically conducted reactions such as, in particular, allyh
Substitutionen, Hydrierungen und Heck-Reaktionen gut geeignet sind (siehe auch Malkov et al, Tetrahedron Letters, 2001, 42, 3045 - 3048; Pfaltz et al., Adv. Synth. Cat, 2003, 345, 33-44; Chelucci et al, Tetrahedron, 2001, 57, 9989-9996, Schleich, Heimchen, Eur. J. Org. Chem., 1999, 2525-2521.Substitutions, hydrogenations and Heck reactions are well suited (see also Malkov et al, Tetrahedron Letters, 2001, 42, 3045 - 3048; Pfaltz et al., Adv. Synth. Cat, 2003, 345, 33-44; Chelucci et al , Tetrahedron, 2001, 57, 9989-9996, Schleich, Heimchen, Eur. J. Org. Chem., 1999, 2525-2521.
Nachteilig an den bislang bekannten Verbindungen ist, dass die Herstellung entweder aufwendig über viele Stufen verläuft, die sterische und elektronische Variation des zentralen Ligandgerüstes schwierig und die Anwendbarkeit für ein breites Substrat- spelrtrum in katalytischen Reaktionen nur selten gegeben ist.Disadvantages of the compounds known to date are that the preparation either takes place in a complex manner over many stages, the steric and electronic variation of the central ligand structure is difficult and the applicability for a wide range of substrates in catalytic reactions is rarely given.
Es bestand daher weiterhin das Bedürfnis, ein in seinen sterischen und elektronischen Eigenschaften leicht variierbares Ligandensystem zu entwickeln, dessen Ubergangsmetallkomplexe als Katalysatoren insbesondere in der asymmetrischen Synthese neben guter Enantioselektivität auch gute Umsatzraten ermöglichen.There was therefore still a need to develop a ligand system which was easy to vary in its steric and electronic properties, the transition metal complexes of which as catalysts, in particular in asymmetric synthesis, not only enabled good enantioselectivity but also good conversion rates.
Es wurden nun Stickstoff-Phosphorverbindungen der Formel (I) gefunden, in derNitrogen-phosphorus compounds of the formula (I) have now been found in the
• *1, *2 jeweils unabhängig voneinander ein stereogenes Kohlenstoffatom markieren, das in R- oder S- Konfiguration vorliegt,• * 1, * 2 each independently mark a stereogenic carbon atom that is in the R or S configuration,
• R1 und R2 jeweils unabhängig voneinander für einen gegebenenfalls substituierten Kohlenwasserstoffrest mit insgesamt 1 bis 18 Kohlenstoffatomen stehen• R 1 and R 2 each independently represent an optionally substituted hydrocarbon radical with a total of 1 to 18 carbon atoms
• Het für gegebenenfalls substituiertes Azoaryl steht und• Het stands for optionally substituted azoaryl and
• A* für einen carbodivalenten, cyclischen und gegebenenfalls substituierten Rest mit insgesamt 5 bis 18 Kohlenstoffatomen steht, der für sich als• A * stands for a carbodivalent, cyclic and optionally substituted radical with a total of 5 to 18 carbon atoms, which as such
Symmetrieelement keine Spiegelebene besitzt.Symmetry element has no mirror plane.
Im Rahmen der Erfindung können alle oben stehenden und im Folgenden aufgeführten, allgemeinen oder in Vorzugsbereichen genannten Restedefinitionen, Para- meter und Erläuterungen untereinander, also auch zwischen den jeweiligen Bereichen und Vorzugsbereichen in beliebiger Weise kombiniert werden.In the context of the invention, all of the radical definitions, parameters and explanations given above and listed below, which are general or mentioned in preferred areas, can be combined with one another in any manner, that is to say also between the respective areas and preferred areas.
Der Begriff „carbodivalent, cyclisch" bedeutet, dass die Bindung des Restes A* zum Rest des Moleküls der Formel (I) über zwei Kohlenstoffatome erfolgt und der Rest A* zumindest einen Cyclus aufweist.The term "carbodivalent, cyclic" means that the bond of the radical A * to the rest of the molecule of the formula (I) takes place via two carbon atoms and the radical A * has at least one cycle.
Alkyl beziehungsweise Alkylen beziehungsweise Alkoxy bedeutet jeweils unabhängig einen geradkettigen, cyclischen, verzweigten oder unverzweigten Alkyl- be- ziehungsweise Alkylen- beziehungsweise Alkoxy-Rest. Gleiches gilt für den nichtaromatischen Teil eines Arylalkyl-Restes.Alkyl or alkylene or alkoxy each independently means a straight-chain, cyclic, branched or unbranched alkyl- or alkylene or alkoxy radical. The same applies to the non-aromatic part of an arylalkyl radical.
Cι-C - Alkyl steht beispielsweise für Methyl, Ethyl, n-Propyl, iso-Propyl, n-Butyl, sec.-Butyl und tert.-Butyl, Cι-C8-Alkyl darüber hinaus beispielsweise für n-Pentyl,C 1 -C 4 -alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl, C 1 -C 8 -alkyl furthermore, for example, n-pentyl,
1-Methylbutyl, 2-Methylbutyl, neo-Pentyl, cyclo-Hexyl, cyclo-Pentyl und n-Hexyl, Cι-C12-Alkyl weiter darüber hinaus beispielsweise für Adamantyl, die isomeren Menthyle, n-Nonyl, n-Decyl und n-Dodecyl, Cι-C2o-Alkyl noch weiter darüber hinaus beispielsweise für n-Hexadecyl und n-Octadecyl.1-methylbutyl, 2-methylbutyl, neo-pentyl, cyclo-hexyl, cyclo-pentyl and n-hexyl, C 1 -C 12 alkyl furthermore, for example, for adamantyl, the isomeric menthyls, n-nonyl, n-decyl and n -Dodecyl, -CC 2 o-alkyl even further, for example, for n-hexadecyl and n-octadecyl.
Cι-C8-Alkoxy steht beispielsweise für Methoxy, Ethoxy, n-Propoxy, iso-Propoxy, n-Butoxy, sec.-Butoxy und tert.-Butoxy, n-Pentoxy, neo-Pentoxy, cyclo-Hexoxy, cyclo-Pentoxy, n-Hexoxy und n-Octoxy, CrC12-Alkoxy weiter darüber hinaus beispielsweise für Adamantoxy, die isomeren Menthoxy-Reste, n-Decoxy und n-Dodecoxy.-C-C 8 alkoxy is, for example, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy and tert-butoxy, n-pentoxy, neo-pentoxy, cyclo-hexoxy, cyclo-pentoxy , n-hexoxy and n-octoxy, CrC 12 alkoxy furthermore for example for adamantoxy, the isomeric menthoxy radicals, n-decoxy and n-dodecoxy.
C2-C20-Alkenyl steht beispielsweise für Vinyl, 1-Propenyl, iso-Propenyl, 1-Butenyl, 1-Hexenyl, 1-Heptenyl, 1-Octenyl oder 2-Octenyl.C 2 -C 20 alkenyl is, for example, vinyl, 1-propenyl, isopropenyl, 1-butenyl, 1-hexenyl, 1-heptenyl, 1-octenyl or 2-octenyl.
Fluoralkyl bedeutet jeweils unabhängig einen geradkettigen, cyclischen, verzweigten oder unverzweigten Alkyl-Rest, der einfach, mehrfach oder vollständig durch Fluoratome substituiert ist.Fluoroalkyl each independently means a straight-chain, cyclic, branched or unbranched alkyl radical which is substituted once, several times or completely by fluorine atoms.
Beispielsweise steht C1-C2o-Fluoralkyl für Trifluormethyl, 2,2,2-Trifluorethyl, Penta- fluorethyl, Nonafluorbutyl, Perfluoroctyl, Perfluordodecyl und Perfluorhexadecyl.For example, C 1 -C 2 o-fluoroalkyl represents trifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, nonafluorobutyl, perfluorooctyl, perfluorododecyl and perfluorohexadecyl.
Aryl steht für einen heteroaromatischen Rest mit 5 bis 18 Gerüstkohlenstoffatomen, in denen keines, ein, zwei oder drei Gerüstkohlenstoffatome pro Cyclus, im gesamtenAryl stands for a heteroaromatic radical with 5 to 18 carbon atoms in which none, one, two or three carbon atoms per cycle, in total
Molekül mindestens jedoch ein Gerüstkohlenstoffatom, durch Heteroatome, ausge- wählt aus der Gruppe Stickstoff, Schwefel oder Sauerstoff, substituiert sein können, vorzugsweise jedoch für einen carbocyclischen aromatischen Rest mit 6 bis 18 Gerüstkohlenstoffatomen.Molecule at least one carbon atom, can be substituted by heteroatoms selected from the group nitrogen, sulfur or oxygen, however, preferably for a carbocyclic aromatic radical having 6 to 18 skeletal carbon atoms.
Beispiele für carbocychsche aromatische Reste mit 6 bis 18 Gerüstkohlenstoffatomen sind zum Beispiel Phenyl, Naphtyl, Phenanthrenyl, Anthracenyl oder Fluorenyl, heteroaromatische Reste mit 5 bis 18 Gerüstkohlenstoffatomen in denen keines, ein, zwei oder drei Gerüstkohlenstoffatome pro Cyclus, im gesamten Molekül mindestens jedoch ein Gerüstkohlenstoffatom, durch Heteroatome, ausgewählt aus der Gruppe Stickstoff, Schwefel oder Sauerstoff, substituiert sein können sind beispielsweise Pyridinyl, Oxazolyl, Benzofuranyl, Dibenzoftrranyl oder Chinolinyl.Examples of carbocyclic aromatic radicals with 6 to 18 carbon atoms are, for example, phenyl, naphthyl, phenanthrenyl, anthracenyl or fluorenyl, heteroaromatic radicals with 5 to 18 carbon atoms in which none, one, two or three carbon atoms per cycle, but at least one carbon atom in the entire molecule , Heteroatoms, selected from the group nitrogen, sulfur or oxygen, may be substituted, for example pyridinyl, oxazolyl, benzofuranyl, dibenzoftrranyl or quinolinyl.
Weiterhin kann der carbocychsche aromatische Rest oder heteroaromatische Rest mit bis zu fünf gleichen oder verschiedenen Substituenten pro Cyclus substituiert sein, die unabhängig voneinander ausgewählt sind aus der Gruppe Chlor, Fluor, C\-Cu- Alkyl, C -C10-Aryl, C5-Cπ -Arylalkyl, Ct-C -Alkoxy, D^CrCs-alky^amino,May further carbocychsche the aromatic radical or heteroaromatic radical with up to five identical or different substituents per cycle be independently selected from the group of chlorine, fluorine, C \ -Cu- alkyl, C -C 10 aryl, C 5 -C π arylalkyl, C t -C alkoxy, D ^ CrCs alky ^ amino,
COO(C C8-Alkyl), CON(Cι-C8-Alkyl)2, COO -Cs-Arylalkyl), COO(C4-C14- Aryl), CO CrCs-Alkyi), C5-Cι5-Arylalkyl oder Tri CrCe-alkyrjsiloxyl.COO (CC 8 alkyl), CON (-C 8 alkyl) 2 , COO -Cs arylalkyl), COO (C 4 -C 14 aryl), CO CrCs alkyl), C 5 -C 5 arylalkyl or Tri CrCe-alkyrjsiloxyl.
Gleiches gilt analog für Aryloxy-Reste.The same applies analogously to aryloxy radicals.
Azoaryl steht für einen heteroaromatischen Rest mit 5 bis 18 Gerüstkohlenstoffatomen, in denen keines, ein, zwei oder drei Gerüstkohlenstoffatome pro Cyclus, im gesamten Molekül mindestens jedoch ein Gerüstkohlenstoffatom, durch Heteroatome substituiert sein können, wobei mindestens ein Stickstoffatom vorhanden sein muss und gegebenenfalls weitere Heteroatome ausgewählt sind aus der Gruppe Stickstoff,Azoaryl represents a heteroaromatic radical with 5 to 18 carbon atoms in which none, one, two or three carbon atoms per cycle, but at least one carbon atom in the entire molecule, but at least one carbon atom, can be substituted by heteroatoms, at least one nitrogen atom and optionally further heteroatoms are selected from the group nitrogen,
Schwefel oder Sauerstoff. Für weitere Substituenten gilt das Gleiche, wie für Aryl oben beschriebenSulfur or oxygen. The same applies to other substituents as described above for aryl
Arylalkyl bedeutet jeweils unabhängig einen geradkettigen, cyclischen, verzweigten oder unverzweigten Alkyl-Rest, der einfach, mehrfach oder vollständig durch Aryl-Arylalkyl each independently means a straight-chain, cyclic, branched or unbranched alkyl radical which can be replaced simply, repeatedly or completely by aryl
Reste gemäß obiger Definition substituiert sein kann. C5-C1 -Arylalkyi steht beispielsweise für Benzyl, 1-Phenylethyl, 1-Phenylpropyl, 2- Phenylpropyl und 1-Naphthylmethyl, sowie gegebenenfalls die isomeren oder stereoisomeren Formen.Residues can be substituted as defined above. C 5 -C 1 arylalkyl is, for example, benzyl, 1-phenylethyl, 1-phenylpropyl, 2-phenylpropyl and 1-naphthylmethyl, and optionally the isomeric or stereoisomeric forms.
Arylalkenyl bedeutet jeweils unabhängig einen geradkettigen, cyclischen, verzweigten oder unverzweigten Alkenyl-Rest, der einfach, mehrfach oder vollständig durch Aryl-Reste gemäß obiger Definition substituiert sein kann.Arylalkenyl each independently means a straight-chain, cyclic, branched or unbranched alkenyl radical which can be substituted once, several times or completely by aryl radicals as defined above.
C6-C1 - Arylalkenyl steht beispielsweise für 1-Phenylvinyl oder 2-Phenylvinyl.C 6 -C 1 arylalkenyl represents, for example, 1-phenylvinyl or 2-phenylvinyl.
Im Folgenden werden die bevorzugten Substitutionsmuster für Verbindungen der Formel (I) definiert:The preferred substitution patterns for compounds of the formula (I) are defined below:
Durch den Umstand, dass A* ein carbodivalenter und cyclischer Rest ist, ist die konformative Beweglichkeit der die Reste Het und PR R2 tragenden Ethylenbrücke üblicherweise stark eingeschränkt. Vorzugsweise sind die Reste Het und PR R transständig zueinander angeordnet.Due to the fact that A * is a carbodivalent and cyclic radical, the conformative mobility of the ethylene bridge carrying the Het and PR R 2 radicals is usually severely restricted. The residues Het and PR R are preferably arranged transposed to one another.
Durch den Umstand, dass die in Formel (T) mit 1 * und 2* bezeichneten Kohlenstoffatome stereogen sind und der Rest A* für sich als Symmetrieelement keine Spiegelebene besitzt, treten die Verbindungen der Formel (T) in Form von Stereoisomeren auf. Von der Erfindung sind sowohl die reinen Stereoisomeren als auch beliebige Mischungen davon umfasst.Due to the fact that the carbon atoms denoted by 1 * and 2 * in formula (T) are stereogenic and the radical A * does not have a mirror plane as an element of symmetry, the compounds of formula (T) occur in the form of stereoisomers. The invention includes both the pure stereoisomers and any mixtures thereof.
Bevorzugt sind stereomerenangereicherte Verbindungen der Formel (I). Stereomeren- angereichert im Sinne der Erfindung bedeutet, dass ein Stereomeres in einem größeren relativen Anteil vorliegt als die jeweils anderen Stereomeren. Dabei können die anderen Stereoisomeren sowohl Enantiomere als auch Diastereomere sein. Bevorzugt beträgt der relative Stoffrnengenanteil nur eines Stereoisomeren bezogen auf die Summe aller Stereoisomeren mindestens 90 %, besonders bevorzugt mindestens 95 % und ganz besonders bevorzugt mindestens 98,5 %.Stereomerically enriched compounds of the formula (I) are preferred. Enriched with stereomers in the sense of the invention means that one stereomer is present in a larger relative proportion than the respective other stereomers. The other stereoisomers can be both enantiomers and diastereomers. The relative amount of substance of only one stereoisomer, based on the sum of all stereoisomers, is preferably at least 90%, particularly preferably at least 95% and very particularly preferably at least 98.5%.
R und R stehen bevorzugt jeweils unabhängig voneinander für: Cι-C2o-Alkyl,R and R are preferably each independently of the other: C 1 -C 2 -alkyl,
CrC2o-Fluoralkyl, C2-C2o-Alkenyl, C4-C24-Aryl, C5-C25-Arylalkyl oder C6-C26- Arylalkenyl oder zusammen für einen cyclischen Rest mit insgesamt 4 bis 20 Kohlenstoffatomen.CrC 2 o-fluoroalkyl, C 2 -C 2 o-alkenyl, C 4 -C 24 aryl, C 5 -C 25 arylalkyl or C 6 -C 26 arylalkenyl or together for a cyclic radical with a total of 4 to 20 carbon atoms ,
R1 und R2' stehen besonders bevorzugt jeweils identisch für: C3-C12- Alkyl, C -C14-R 1 and R 2 ' are particularly preferably each identical: C 3 -C 12 -alkyl, C -C 14 -
Aryl, C5-C13- Arylalkyl oder zusammen für -Cs-Alkylen.Aryl, C 5 -C 13 arylalkyl or together for -Cs-alkylene.
R und R >2 stehen ganz besonders bevorzugt jeweils identisch für: iso-Propyl, tert.- Butyl, Cyclohexyl, Phenyl, 2-(C1-C8)-alkylphenyl wie o-Tolyl, 3-(C1-C8)-alkylphenyl wie m-Tolyl, 4-(C1-C8)-alkylphenyl wie p-Tolyl, 2,6-Di-(C1-C8)-alkylphenyl wie 2,6-R and R> 2 very particularly preferably each represent: iso-propyl, tert-butyl, cyclohexyl, phenyl, 2- (C 1 -C 8 ) alkylphenyl such as o-tolyl, 3- (C 1 -C 8 ) -alkylphenyl such as m-tolyl, 4- (C 1 -C 8 ) -alkylphenyl such as p-tolyl, 2,6-di- (C 1 -C 8 ) -alkylphenyl such as 2,6-
Dimethylphenyl, 2,4-Di-(C1-C8)-alkylphenyl wie 2,4-Dimethylphenyl, 3,5-Di-(C\- C8)-alkylphenyl wie 3,5-Dimethylphenyl, 3,4,5-Tri-(C1-C8)-alkylphenyl wie Mesityl und Isityl, 2-(C1-C8)-Alkoxyphenyl wie o-Anisyl und o-Phenetyl, 3-(Cι.-C8)- Alkoxyphenyl wie m-Anisyl und m-Phenetyl, 4-(Cι-C8)~Alkoxyphenyl wie p-Anisyl und p-Phenetyl, 2,4-Di-(Cι-C8)-alkoxyphenyl wie 2,4-Dimethoxyphenyl, 2,6-Di-(C1-Dimethylphenyl, 2,4-di (C 1 -C 8 ) alkylphenyl such as 2,4-dimethylphenyl, 3,5-di (C \ - C 8 ) alkylphenyl such as 3,5-dimethylphenyl, 3,4, 5-tri- (C 1 -C 8 ) alkylphenyl such as mesityl and isityl, 2- (C 1 -C 8 ) alkoxyphenyl such as o-anisyl and o-phenetyl, 3- (Cι.-C 8 ) - alkoxyphenyl such as m-anisyl and m-phenetyl, 4- (Cι-C 8 ) ~ alkoxyphenyl such as p-anisyl and p-phenetyl, 2,4-di- (Cι-C 8 ) alkoxyphenyl such as 2,4-dimethoxyphenyl, 2, 6-Di- (C 1 -
C8)-alkoxyphenyl wie 2,6-Dimethoxyphenyl, 3,5-Di-(Cι-C8)-Alkoxyphenyl wie 3,5- Di ethoxyphenyl, 3,4,5-Tri-(C -C8)-alkoxyphenyl wie 3,4,5-Trimethoxyphenyl, 3,5- Dialkyl-4-(C1-C8)-alkoxyphenyl wie 3,5-Dimethyl-4-anisyl, 3,5-(C1-C8)-Dialkyl-4- di-(CrC8)-alkylaminophenyl, 3,5-Dimethyl-4-dimethylamino-phenyl, 4-Di-(Ci-C8)- alkylaminophenyl wie 4-Diethylaminophenyl und 4-Dimethylaminophenyl, 3,5-Bis-C 8 ) -alkoxyphenyl such as 2,6-dimethoxyphenyl, 3,5-di- (-C-C 8 ) alkoxyphenyl such as 3,5-di ethoxyphenyl, 3,4,5-tri- (C -C 8 ) alkoxyphenyl such as 3,4,5-trimethoxyphenyl, 3,5-dialkyl-4- (C 1 -C 8 ) alkoxyphenyl such as 3,5-dimethyl-4-anisyl, 3,5- (C 1 -C 8 ) dialkyl -4- di- (CrC 8 ) -alkylaminophenyl, 3,5-dimethyl-4-dimethylamino-phenyl, 4-di- (Ci-C 8 ) -alkylaminophenyl such as 4-diethylaminophenyl and 4-dimethylaminophenyl, 3,5-bis -
[(C1-C4)-fluoralkyl]phenyl wie 3,5-Bis-trifluormethylρhenyl, 2,4-Bis-[(Cι-C4)-fluor- alkyl]phenyl wie 2,4-Bis-trifluormethylρhenyl, 4-[(C1-C4)-Fluoralkyl]phenyl wie 4- Trifluormethylphenyl und ein-, zwei- drei-, vier- oder fnnffach durch Fluor und/oder Chlor substituiertes Phenyl, Fluorenyl oder Naphthyl wie 4-Fluorphenyl und 4-Chlor- phenyl sowie Furanyl. Bevorzugt steht Azoaryl für 2-Pyridyl oder 2- Chinolyl, wobei die genannten Reste weiterhin durch einen, zwei oder drei Reste substituiert sein können, die jeweils unabhängig voneinander ausgewählt sind aus der Gruppe Chlor, Brom, Fluor, Cι-C12- Alkyl, C4-Cιo-AryL C5-Cn -Arylalkyl und C C12-Alkoxy.[(C 1 -C 4 ) -fluoroalkyl] phenyl such as 3,5-bis-trifluoromethyl-phenyl, 2,4-bis - [(-C-C 4 ) -fluoro-alkyl] phenyl such as 2,4-bis-trifluoromethyl-phenyl, 4 - [(C 1 -C 4 ) -fluoroalkyl] phenyl such as 4-trifluoromethylphenyl and phenyl substituted by one, two, three, four or five times by fluorine and / or chlorine, fluorenyl or naphthyl such as 4-fluorophenyl and 4-chlorine - phenyl and furanyl. Azoaryl is preferably 2-pyridyl or 2-quinolyl, it being possible for the radicals mentioned to be further substituted by one, two or three radicals which are each independently selected from the group chlorine, bromine, fluorine, C 1 -C 12 -alkyl, C 4 -Cιo-AryL C 5 -C n arylalkyl and CC 12 alkoxy.
Ganz besonders bevorzugt steht Azoaryl für 2-Pyridyl, 6-Brom-2-pyridyl, 6-Phenyl- 2-pyridyl und 2-Chinolyl.Azoaryl very particularly preferably represents 2-pyridyl, 6-bromo-2-pyridyl, 6-phenyl-2-pyridyl and 2-quinolyl.
Besonders bevorzugte Verbindungen der Formel (I) sind solche der Formeln (la) und (1b)Particularly preferred compounds of the formula (I) are those of the formulas (Ia) and (1b)
(la) (Ib)(la) (Ib)
in denenin which
R , R und Het die vorstehend angegebenen Bedeutungen und Vorzugsbereiche besitzen.R, R and Het have the meanings and preferred ranges given above.
Als Verbindungen der Formel (I) seien genannt: 2-[(lS,2i?,3i?,4S)-3-( iphenylphosphino)-l,7,7-trimethylbicyclo[2.2.1]hept-2-yl]- pyridin,The following may be mentioned as compounds of the formula (I): 2 - [(IS, 2i?, 3i?, 4S) -3- (iphenylphosphino) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] - pyridine,
2-[(lS,2i?,3S,4S)-3- iphenylphospMno)-l,7,7-trimethylbicyclo[2.2.1]-hept-2-yl]-6- phenyl-pyridin,2 - [(IS, 2i?, 3S, 4S) -3- iphenylphospMno) -l, 7,7-trimethylbicyclo [2.2.1] -hept-2-yl] -6-phenylpyridine,
2-[(lS,2i-,3Ä,4S)-3-(Dicyclohexylphosphino)-l,7,7-trimethylbicyclo[2.2.1]hept-2- yl]-pyridin, 2-[(lS,2i?,3S,4S)-3-(Diphenylphosphino)-l,7,7-tri-methyl-bicyclo-[2.2.1]hept-2-yl]- chinolin,2 - [(IS, 2i, 3A, 4S) -3- (dicyclohexylphosphino) -1,7,7-trimethylbicyclo [2.2.1] hept-2-yl] pyridine, 2 - [(IS, 2i?, 3S, 4S) -3- (diphenylphosphino) -l, 7,7-tri-methyl-bicyclo- [2.2.1] hept-2-yl] - quinoline,
2-[(lS,2i?,3S,5i?)-3-piphenylphosphino)-6,6-dimethyl-bicyclo[3.1.1]hept-2-yl]- pyridin und2 - [(IS, 2i?, 3S, 5i?) - 3-piphenylphosphino) -6,6-dimethyl-bicyclo [3.1.1] hept-2-yl] pyridine and
2-[(lS,2i?,3S,5i?)-3-(Diphenyl-phosphino)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]-6- phenyl-pyridin.2 - [(IS, 2i?, 3S, 5i?) - 3- (Diphenyl-phosphino) -6,6-dimethylbicyclo [3.1.1] hept-2-yl] -6-phenyl-pyridine.
Die Verbindungen der Formel (I) beziehungsweise (la) und (Ib) können beispielsweise ausgehend von Verbindungen der Formel (II) gemäß nachstehendem Schema hergestellt werden.The compounds of the formula (I) or (la) and (Ib) can be prepared, for example, starting from compounds of the formula (II) according to the scheme below.
Schritt a)Step a)
(II) (III) (IV)(II) (III) (IV)
Schritt b)Step b)
(IV (V) (I)(IV (V) (I)
In den Formeln (IT), (III), (IV) und (V) besitzen 1*, 2*, R1, R2, Het und A* jeweils die vorstehend angegebenen Bedeutungen und Norzugsbereiche,In the formulas (IT), (III), (IV) and (V) 1 *, 2 *, R 1 , R 2 , Het and A * each have the meanings and ranges specified above,
X1 und X2 stehen jeweils unabhängig voneinander für Chlor, Brom, lod oder ein Sulfonat, bevorzugt für Brom, lod oder ein C1-C -Perfluoralkylsulfonat. Die Metallierung kann beispielsweise so erfolgen, dass die Verbindungen der Formel (DI) in an sich bekannter Weise in eine analoge Organozink- oder Organo- magnesiumverbindung überfuhrt werden und diese dann mit Verbindungen der Formel (H) in Gegenwart von Katalysator zu Verbindungen der Formel (IN) umgesetzt werden. Als Katalysator im Schritt a) können beispielsweise Palladium- oder Νickelkomplexe eingesetzt werden.X 1 and X 2 each independently represent chlorine, bromine, iodine or a sulfonate, preferably bromine, iodine or a C 1 -C -perfluoroalkyl sulfonate. The metalation can be carried out, for example, in such a way that the compounds of the formula (DI) are converted in a manner known per se into an analogous organozinc or organomagnesium compound and this is then reacted with compounds of the formula (H) in the presence of a catalyst to give compounds of the formula ( IN) are implemented. Palladium or nickel complexes, for example, can be used as the catalyst in step a).
Die Verbindungen der Formel (IN) sind als wertvolle Intermediate für Nerbindungen der Formel (I) von der Erfindung ebenfalls umfasst. Dabei gelten alle genannten Bereiche und Vorzugsbereiche für Het und A* analog.The compounds of the formula (IN) are also encompassed by the invention as valuable intermediates for the compounds of the formula (I). All mentioned areas and preferred areas for Het and A * apply analogously.
Bevorzugte Nerbindungen der Formel (IN) sind solche der Formeln (INa) und (INb):Preferred compounds of the formula (IN) are those of the formulas (INa) and (INb):
(IVa) (IVb)(IVa) (IVb)
in denenin which
Het die unter der Formel (I) genannte Bedeutung und deren Norzugsbereiche besitzt.Het has the meaning given under the formula (I) and its ranges.
Als Einzelverbindungen seien genannt:The following may be mentioned as individual connections:
(2-[(li?,4i?)-l ,7,7-Trimethylbicyclo[2.2. l]hept-2-en-2-yl]pyridin,(2 - [(li?, 4i?) - l, 7,7-trimethylbicyclo [2.2. L] hept-2-en-2-yl] pyridine,
2-Brom-6-[(li?,4i?)-l,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl]pyridin,2-bromo-6 - [(? Li, 4i?) - l, 7,7-trimethylbicyclo [2.2.1] hept-2-en-2-yl] pyridine,
2-[(li?,4i-)-l,7,7-Trimethylbicyclo[2.2.1]hept-2-en-2-yl]chinolin,2 - [(li, 4i -?) - l, 7,7-trimethylbicyclo [2.2.1] hept-2-en-2-yl] quinoline,
2-[(li?,5S)-6,6-Dimethylbicyclo[3.1.1 ]hept-2-en-2-yl]pyridin,2 - [(li?, 5S) -6,6-dimethylbicyclo [3.1.1] hept-2-en-2-yl] pyridine,
2-Brom-6-[(li?,5S)-6,6-dimethylbicyclo[3.1. l]hept-2-en-2-yl]pyridin, 2-Phenyl-6-[(li?,4i?)-l,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl]ρyridin und 2-[(li?,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl]-6-phenylpyridin.(, Li 5S?) [-6,6-dimethyl [3.1 - 2-bromo-sixth l] hept-2-en-2-yl] pyridine, 2-phenyl-6 - [(li?, 4i?) - l, 7,7-trimethylbicyclo [2.2.1] hept-2-en-2-yl] ρyridine and 2 - [(li?, 5S) -6 , 6-dimethylbicyclo [3.1.1] hept-2-en-2-yl] -6-phenylpyridine.
Schritt b) kann derart erfolgen, dass Nerbindungen der Formel (N) in Gegenwart einer Base, die die Nerbindungen der Formel (N) zumindest teilweise deprotonieren kann in Gegenwart eines Lösungsmittels zu Verbindungen der Formel (I) umgesetzt werden.Step b) can be carried out in such a way that Nerbindungen of formula (N) in the presence of a base, which can at least partially deprotonate the Nerbindungen of formula (N) in the presence of a solvent to compounds of formula (I).
Bevorzugte Basen sind Alkoholate, bevorzugte Lösungsmittel Sulfoxide wie bei- spiels weise Dimethylsulfoxid, Sulfone wie zum Beispiel Tetramethylensulfon oder sekundäre Carbonsäureamide wie Dimethylformamid oder Ν-Methylpyrrolidon.Preferred bases are alcoholates, preferred solvents sulfoxides such as dimethyl sulfoxide, sulfones such as tetramethylene sulfone or secondary carboxamides such as dimethylformamide or Ν-methylpyrrolidone.
Besonders vorteilhaft ist die von Knöchel et al. in Tetrahedron Letters, 2002, 43, 5817-5819 beschriebene Methode mit Kalium-tert.-butanolat als Base und Dimethyl- sulfoxid als Lösungsmittel.The one described by Knöchel et al. in Tetrahedron Letters, 2002, 43, 5817-5819 described method with potassium tert-butoxide as a base and dimethyl sulfoxide as a solvent.
Alternativ zu Schritt b) kann man gemäß nachstehendem Schema in einem Schritt c) die Verbindungen der Formel (IN) durch Umsetzung mit Nerbindungen der Formel (NT) zu Nerbindungen der Formel (NU) umsetzen und in einem Schritt d) die Nerbindungen der Formel (VIT) zu Verbindungen der Formel (I) reduzieren.As an alternative to step b), the compounds of the formula (IN) can be reacted according to the following scheme in a step c) by reaction with Nerbindungen of the formula (NT) to Nerbindungen of the formula (NU) and in a step d) the Nerbindungen of the formula ( VIT) to reduce compounds of formula (I).
Schritt c)Step c)
(IV) ( I) (VII) Schritt d) (IV) (I) (VII) Step d)
Reduktionreduction
H H
(VII) (I)(VII) (I)
Schritt c) kann dabei völlig analog zu Schritt b) durchgeführt werden, Schritt d) in an sich bekannter Weise beispielsweise durch Reduktion mit Silanen wie insbesondere Trichlorsilan in Gegenwart einer Base wie insbesondere Triethylamin.Step c) can be carried out completely analogously to step b), step d) in a manner known per se, for example by reduction with silanes such as in particular trichlorosilane in the presence of a base such as in particular triethylamine.
Das Verfahren, das die Schritte c) und d) umfasst kann insbesondere bei Einsatz elektronenreicher Phosphane der Formel (IJT) von Vorteil sein.The method comprising steps c) and d) can be of advantage in particular when using electron-rich phosphines of the formula (IJT).
Die Verbindungen der Formel (VIT) sind als wertvolle Intermediate für Verbindungen der Formel (I) von der Erfindung ebenfalls umfasst. Dabei gelten alle genannten Bereiche und Vorzugsbereiche für Het und A* analog.The compounds of the formula (VIT) are also encompassed by the invention as valuable intermediates for compounds of the formula (I). All mentioned areas and preferred areas for Het and A * apply analogously.
Bevorzugte Verbindungen der Formel (VIT) sind solche der Formeln (Vlla) undPreferred compounds of the formula (VIT) are those of the formulas (VIIa) and
(Vlla) (Vllb)(Vlla) (Vllb)
in denenin which
R » 1 , τ R> 2 und Het die vorstehend angegebenen Bedeutungen und Vorzugsbereiche besitzen. Als Einzelverbindungen der Formeln (NITa) und (NITb) seien genannt: 2-[(lS,2S,3i?,4S)-3-(Diphenylphosphoryl)-l,7,.7-trimethylbicyclo[2.2.1]hept-2- yl]pyridin, 2-[(lS,2i?,3S,4S)-3-(Diphenylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept-2-yl]-6- phenylpyridin,R »1, τ R> 2 and Het have the meanings and preferred ranges given above. The following may be mentioned as individual compounds of the formulas (NITa) and (NITb): 2 - [(IS, 2S, 3i?, 4S) -3- (diphenylphosphoryl) -l, 7, .7-trimethylbicyclo [2.2.1] hept-2 - yl] pyridine, 2 - [(IS, 2i?, 3S, 4S) -3- (diphenylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] -6- phenylpyridine,
2-[(lS,2S,3i?,4S)-3-(Dicyclohexylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept-2- yljpyridin, 2-[(lS,2S,3i?,4S)-3-(Diphenylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept-2- yljchinolin,2 - [(IS, 2S, 3i?, 4S) -3- (dicyclohexylphosphoryl) -1, 7,7-trimethylbicyclo [2.2.1] hept-2-ylpyridine, 2 - [(IS, 2S, 3i?, 4S ) -3- (Diphenylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-ylquinoline,
2-[(lS,2i?,3S,5i-)-3-(Diphenylρhosphoryl)-6,6-dimethylbicyclo[3.1.1]hept-2- yljpyridin und2 - [(IS, 2i?, 3S, 5i -) - 3- (Diphenylρhosphoryl) -6,6-dimethylbicyclo [3.1.1] hept-2-ylpyridine and
2-[(lS,2i?,3S,5i?)-3-(Diρhenylphosphoryl)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]-6- phenyl-pyridin.2 - [(IS, 2i?, 3S, 5i?) - 3- (Diρhenylphosphoryl) -6,6-dimethylbicyclo [3.1.1] hept-2-yl] -6-phenyl-pyridine.
Die Erfindung umfasst weiterhin Ubergangsmetallkomplexe, die die erfindungsgemäßen Nerbindungen der Formel (I) enthalten. Ubergangsmetallkomplexe, die stereoisomerenangereicherte Nerbindungen der Formel (I) enthalten, sind bevorzugt.The invention furthermore comprises transition metal complexes which contain the compound of the formula (I) according to the invention. Transition metal complexes which contain stereoisomerically enriched Nerbindungen of formula (I) are preferred.
Ubergangsmetallkomplexe sind bevorzugt Komplexe von Ruthenium, Osmium,Transition metal complexes are preferably complexes of ruthenium, osmium,
Cobalt, Rhodium, Iridium, Nickel, Palladium, Platin und Kupfer, besonders bevorzugt Komplexe von Ruthenium, Rhodium, Iridium, Nickel und Palladium und besonders bevorzugt Komplexe von Palladium und Iridium.Cobalt, rhodium, iridium, nickel, palladium, platinum and copper, particularly preferably complexes of ruthenium, rhodium, iridium, nickel and palladium and particularly preferably complexes of palladium and iridium.
Die erfindungsgemäßen Ubergangsmetallkomplexe eignen sich insbesondere alsThe transition metal complexes according to the invention are particularly suitable as
Katalysatoren. Daher sind von der Erfindung auch Katalysatoren umfasst, die die erfindungsgemäßen Ubergangsmetallkomplexe enthalten.Catalysts. The invention therefore also includes catalysts which contain the transition metal complexes according to the invention.
Als Katalysatoren können beispielsweise entweder isolierte Übergangsmetall- komplexe eingesetzt werden oder solche Ubergangsmetallkomplexe, die durch Um- setzung von Übergangsmetallverbindungen und Nerbindungen der Formel (I) erhältlich sind.Either isolated transition metal complexes or those transition metal complexes which are converted by Settlement of transition metal compounds and Nerbindungen of formula (I) are available.
Isolierte Ubergangsmetallkomplexe, die die Nerbindungen der Formel (I) enthalten, sind vorzugsweise solche, in denen das Verhältnis von Übergangsmetall zu Verbindung der Formel (I) 1 : 1 betragt.Isolated transition metal complexes which contain the Nerbindungen of formula (I) are preferably those in which the ratio of transition metal to compound of formula (I) is 1: 1.
Bevorzugt sind dabei die erfindungsgemäßen Verbindungen der Formel (VIII)The compounds of the formula (VIII) according to the invention are preferred
[©L^MjAn (vπr)[© L ^ MjAn (vπr)
in der (I) für Verbindungen der Formel (I) mit der dort genannten Bedeutung und deren Vorzugsbereichen steht undin which (I) stands for compounds of the formula (I) with the meaning given therein and their preferred ranges and
M für Rhodium oder Iridium undM for rhodium or iridium and
L1 jeweils für ein C2-C12- Alken wie beispielsweise Ethylen oder Cycloocten oder ein Νitril wie beispielsweise Acetonitril, Benzonitril oder Benzylnitril steht, oderL 1 in each case represents a C 2 -C 12 alkene such as, for example, ethylene or cyclooctene or a nitrile such as, for example, acetonitrile, benzonitrile or benzyl nitrile, or
L] 2 zusammen für ein (C4-Cι2)-Dien wie beispielsweise Bicyclo[2.1.1]hepta-2,5- dien (Νorbornadien) oder 1,5-Cyclooctadien steht undL ] 2 together represents a (C 4 -C 2 ) -diene such as, for example, bicyclo [2.1.1] hepta-2,5-diene (Νorbornadiene) or 1,5-cyclooctadiene and
An für ein nicht oder schwach koordinierendes Anion wie zum Beispiel Methan- sulfonat, Trifluormethansulfonat, Tetrafluoroborat, Hexafluorophosphat,An for a non or weakly coordinating anion such as methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate,
Perchlorat, Hexafluoroantimonat, Tetra(bis-3,5-trifluromethylphenyl)-borat oder Tetraphenylborat steht.Perchlorate, hexafluoroantimonate, tetra (bis-3,5-trifluromethylphenyl) borate or tetraphenyl borate.
Bevorzugte Ubergangsmetallkomplexe sind jedoch solche, die durch Umsetzung von Übergangsmetall Verbindungen und Verbindungen der Formel (I) erhältlich sind. Geeignete Übergangsmetallverbindungen sind beispielsweise solche der FormelHowever, preferred transition metal complexes are those which can be obtained by reacting transition metal compounds and compounds of the formula (I). Suitable transition metal compounds are, for example, those of the formula
M(An!)q (LXa)M (An ! ) Q (LXa)
in derin the
M für Rhodium, Iridium, Ruthenium, Nickel, Palladium, Platin oder Kupfer undM for rhodium, iridium, ruthenium, nickel, palladium, platinum or copper and
An1 für Chlorid, Bromid, Acetat, Nitrat, Methansulfonat, Trifluormethansulfonat oder Acetylacetonat undAn 1 for chloride, bromide, acetate, nitrate, methanesulfonate, trifluoromethanesulfonate or acetylacetonate and
q für Rhodium, Iridium und Ruthenium für 3, für Nickel, Palladium und Platin für 2 und für Kupfer für 1 steht,q stands for rhodium, iridium and ruthenium for 3, for nickel, palladium and platinum for 2 and for copper for 1,
oder Übergangsmetallverbindungen der allgemeinen Formel (LXb)or transition metal compounds of the general formula (LXb)
M(An2)qL1 2 (LXb)M (An 2 ) q L 1 2 (LXb)
in derin the
M für Ruthenium, Iridium, Ruthenium, Nickel, Palladium, Platin oder Kupfer undM for ruthenium, iridium, ruthenium, nickel, palladium, platinum or copper and
An2 für Chlorid, Bromid, Acetat, Methansulfonat oder Trifluormethansulfonat, Tetrafluoroborat oder Hexafluorophosphat, Perchlorat, Hexafluoroantimonat,An 2 for chloride, bromide, acetate, methanesulfonate or trifluoromethanesulfonate, tetrafluoroborate or hexafluorophosphate, perchlorate, hexafluoroantimonate,
Tetra(bis-3,5-trifluromethylphenyl)-borat oder Tetraphenylborat steht undTetra (bis-3,5-trifluromethylphenyl) borate or tetraphenylborate and
q für Rhodium und Iridium für 1, für Ruthenium, Nickel, Palladium und Platin für 2 und für Kupfer für 1 steht, L1 jeweils für ein C2-C12-Alken wie beispielsweise Ethylen oder Cycloocten oder ein Nitril wie beispielsweise Acetonitril, Benzonitril oder Benzylnitril steht, oderq stands for rhodium and iridium for 1, for ruthenium, nickel, palladium and platinum for 2 and for copper for 1, L 1 each represents a C 2 -C 12 alkene such as, for example, ethylene or cyclooctene or a nitrile such as, for example, acetonitrile, benzonitrile or benzyl nitrile, or
L 2 zusammen für ein (C4-C12)-Dien wie beispielsweise Bicyclo[2.1.1]hepta-2,5- dien (Norbornadien) oder 1,5-Cyclooctadien stehtL 2 together represents a (C 4 -C 12 ) diene such as, for example, bicyclo [2.1.1] hepta-2,5-diene (norbornadiene) or 1,5-cyclooctadiene
oder Übergangsmetallverbindungen der Formel (LXc)or transition metal compounds of the formula (LXc)
[ML2Anλ 2]2 (LXc)[ML 2 An λ 2 ] 2 (LXc)
in derin the
M für Ruthenium undM for ruthenium and
L2 für Arylreste wie zum Beispiel Cymol, Mesityl, phenyl oder Cyclooctadien, Norbornadien oder Methylallyl stehtL 2 represents aryl radicals such as, for example, cymol, mesityl, phenyl or cyclooctadiene, norbornadiene or methylallyl
oder Übergangsmetallverbindungen der Formel (LXd)or transition metal compounds of the formula (LXd)
[M(L3)2]An4 (TXd)[M (L 3 ) 2 ] To 4 (TXd)
in derin the
M für Iridium oder Rhodium undM for iridium or rhodium and
L3 für (C4-C12)-Dien wie beispielsweise Bicyclo[2.1.1]hepta-2,5-dien (Norbornadien) oder 1,5-Cyclooctadien steht undL 3 stands for (C 4 -C 12 ) diene such as, for example, bicyclo [2.1.1] hepta-2,5-diene (norbornadiene) or 1,5-cyclooctadiene and
An4 für ein nicht oder schwach koordinierendes Anion wie zum Beispiel Methansulfonat, Trifluormethansulfonat, Tetrafluoroborat, Hexafluorophosphat, Perchlorat, Hexafluoroantimonat, Tetra(bis-3,5-trifluromethylphenyl)-borat oder Tetraphenylborat steht.An 4 for a non or weakly coordinating anion such as methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate, Perchlorate, hexafluoroantimonate, tetra (bis-3,5-trifluromethylphenyl) borate or tetraphenyl borate.
Darüber hinaus sind als Übergangsmetallverbindungen beispielsweise Ni(l,5-Cyclo- octadien)2, Pd2(dibenzylidenaceton)3, Pd[PPh3] , Cyclopentadienyl2Ru,In addition, the transition metal compounds are, for example, Ni (1,5-cyclo-octadiene) 2 , Pd 2 (dibenzylidene acetone) 3 , Pd [PPh 3 ], cyclopentadienyl 2 Ru,
Rh(acac)(CO)2, fr(pyridin)2(l,5-Cyclooctadien), Cu(Phenyl)Br, Cu(Phenyl)Cl, Cu(Phenyl)I, Cu(PPh3)2Br, [Cu(CH3CN)4]BF4 und [Cu(CH3CN)4]PF6 oder mehr- kernige verbrückte Komplexe wie beispielsweise [Rh(l,5-cyclooctadien)Cl]2, [Rh(l,5-cyclooctadien)Br]2, [Rh(Ethen)2Cl]2, [Rh(Cycloocten)2Cl]2 geeignet.Rh (acac) (CO) 2 , fr (pyridine) 2 (1,5-cyclooctadiene), Cu (phenyl) Br, Cu (phenyl) Cl, Cu (phenyl) I, Cu (PPh3) 2 Br, [Cu ( CH 3 CN) 4 ] BF 4 and [Cu (CH 3 CN) 4 ] PF 6 or multinuclear bridged complexes such as [Rh (1,5-cyclooctadiene) Cl] 2 , [Rh (1,5-cyclooctadiene) Br] 2 , [Rh (ethene) 2Cl] 2 , [Rh (cyclooctene) 2 Cl] 2 are suitable.
Bevorzugt werden als Übergangsmetallverbindungen eingesetzt: [Rh(cod)Cl]2, [Rh(cod)Br]2, [Rh(cod)2]ClO4, [Rh(cod)2]BF4, [Rh(cod)2]PF4, [Rh(cod)2]ClO6, [Rh(cod)2]OTf, [Rh(cod)2]BARF (Ar = 3,5-bistriπuormethyl- phenyl), [Rh(cod)2]SbF6, RuCl2(cod), [(Cymol)RuCl2]2, [(Benzol)RuCl2]2, [(Mesityl)RuCl2]2, [(Cymol)RuBr2]2, [(Cymol)RuI2]2, [(Cymol)Ru(BF4)2]2,The following are preferably used as transition metal compounds: [Rh (cod) Cl] 2 , [Rh (cod) Br] 2 , [Rh (cod) 2 ] ClO 4 , [Rh (cod) 2 ] BF 4 , [Rh (cod) 2 ] PF 4 , [Rh (cod) 2 ] ClO 6 , [Rh (cod) 2 ] OTf, [Rh (cod) 2 ] BARF (Ar = 3,5-bistriπuormethylphenyl), [Rh (cod) 2 ] SbF 6 , RuCl 2 (cod), [(Cymol) RuCl 2 ] 2 , [(benzene) RuCl 2 ] 2 , [(Mesityl) RuCl 2 ] 2 , [(Cymol) RuBr 2 ] 2 , [(Cymol) RuI 2 ] 2 , [(Cymol) Ru (BF 4 ) 2 ] 2 ,
[(Cymol)Ru(PF6)2]2, [(Cymol)Ru(BARF)2]2 (Ar = 3,5-bistrifluormethylphenyl), [(Cymol)Ru(SbF6)2]2, [Ir(cod)Cl]2, [Ir(cod)2]PF6, [Ir(cod)2]ClO4, [Lr(cod)2]SbF6, [Ir(cod)2]BF4, [Ir(cod)2]OTf, [rr(cod)2]BARF (Ar = 3,5-bistrifluormethylphenyl), RuCl3, NiCl3, RhCl3, PdCl2, PdBr2, Pd(OAc)2, Pd2(dibenzylidenaceton)3, Pd(acetylacetonat)2, CuOTf, Cul, CuCl, Cu(OTf)2, CuBr, Cul, CuBr2, CuCl2, Cul2,[(Cymol) Ru (PF 6 ) 2 ] 2 , [(Cymol) Ru (BARF) 2 ] 2 (Ar = 3,5-bistrifluoromethylphenyl), [(Cymol) Ru (SbF 6 ) 2 ] 2 , [Ir ( cod) Cl] 2 , [Ir (cod) 2 ] PF 6 , [Ir (cod) 2 ] ClO 4 , [Lr (cod) 2 ] SbF 6 , [Ir (cod) 2 ] BF 4 , [Ir (cod ) 2 ] OTf, [rr (cod) 2 ] BARF (Ar = 3,5-bistrifluoromethylphenyl), RuCl 3 , NiCl 3 , RhCl 3 , PdCl 2 , PdBr 2 , Pd (OAc) 2, Pd 2 (dibenzylidene acetone) 3 , Pd (acetylacetonate) 2 , CuOTf, Cul, CuCl, Cu (OTf) 2 , CuBr, Cul, CuBr 2 , CuCl 2 , Cul 2 ,
[Rh(nbd)Cl]2, [Rh(nbd)Br]2, [Rh(nbd)2]ClO4, [Rh(nbd)2]BF4, [Rh(nbd)2]PF6, [Rh(nbd)2]OTf, [Rh(nbd)2]BARF (Ar = 3,5-bistrifluormethylphenyl), [Rh(nbd)2]SbF6, RuCl2(nbd), [Ir(nbd)2]PF6, [Ir(nbd)2]ClO4, [Ir(nbd)2]SbF6, [Ir(nbd)2]BF4, [Ir(nbd)2]OTf, [Ir(nbd)2]BARF (Ar = 3,5-bistrifluormethylphenyl), Ir(pyridin)2(nbd), [Ru(DMSO) Cl2], [Ru(CH3CN)4Cl2], [Ru(PhCN)4Cl2],[Rh (nbd) Cl] 2 , [Rh (nbd) Br] 2 , [Rh (nbd) 2 ] ClO 4 , [Rh (nbd) 2 ] BF 4 , [Rh (nbd) 2 ] PF 6 , [Rh (nbd) 2 ] OTf, [Rh (nbd) 2 ] BARF (Ar = 3,5-bistrifluoromethylphenyl), [Rh (nbd) 2 ] SbF 6 , RuCl 2 (nbd), [Ir (nbd) 2 ] PF 6 , [Ir (nbd) 2 ] ClO 4 , [Ir (nbd) 2 ] SbF 6 , [Ir (nbd) 2 ] BF 4 , [Ir (nbd) 2 ] OTf, [Ir (nbd) 2 ] BARF (Ar = 3,5-bistrifluoromethylphenyl), Ir (pyridine) 2 (nbd), [Ru (DMSO) Cl 2 ], [Ru (CH 3 CN) 4 Cl 2 ], [Ru (PhCN) 4 Cl 2 ],
[Ru(cod)Cl2]n, [Ru(cod)4(Methallyl)2], [Ru(acetylacetonat)3][Ru (cod) Cl 2 ] n , [Ru (cod) 4 (methallyl) 2 ], [Ru (acetylacetonate) 3 ]
Noch weiter bevorzugt sind [Ir(cod)Cl]2, [Ir(cod)2]PF6, [Ir(cod)2]ClO4, [Ir(cod)2]SbF6, [Ir(cod)2]BF4, [Ir(cod)2]OTf, [Ir(cod)2]BARF (BARF = 3,5-bis- trifluormethylphenyl). Die Menge der eingesetzten Übergangsmetallverbindungen kann bezogen auf denEven more preferred are [Ir (cod) Cl] 2 , [Ir (cod) 2 ] PF 6 , [Ir (cod) 2 ] ClO 4 , [Ir (cod) 2 ] SbF 6 , [Ir (cod) 2 ] BF 4 , [Ir (cod) 2 ] OTf, [Ir (cod) 2 ] BARF (BARF = 3,5-bis-trifluoromethylphenyl). The amount of transition metal compounds used can be based on the
Gehalt an Metall beispielsweise 25 bis 200 mol.-% bezogen auf die eingesetzteMetal content, for example 25 to 200 mol% based on the one used
Verbindung der Formel (I) betragen, bevorzugt sind 50 bis 150 mol.-%, ganz be- sonders bevorzugt 75 bis 125 mol.-% und noch weiter bevorzugt 100 bis 115 mol.-%.Compound of the formula (I) are preferably 50 to 150 mol%, very particularly preferably 75 to 125 mol% and even more preferably 100 to 115 mol%.
Die Katalysatoren, die die erfindungsgemäßen Ubergangsmetallkomplexe enthalten eignen sich insbesondere für 1,4- Additionen, allylische Substitutionen, Hydro- borierungen, Hydroformylieiungen, Hydrocyanierungen, Heck-Reaktionen und Hydrogenierungen.The catalysts which contain the transition metal complexes according to the invention are particularly suitable for 1,4-additions, allylic substitutions, hydroboration, hydroformylation, hydrocyanation, Heck reactions and hydrogenation.
Enthalten die Katalysatoren Ubergangsmetallkomplexe die stereoisomerenange- reicherte Verbindungen der Formel (I) enthalten, eignen sich die Katalysatoren insbesondere für die asymmetrische Durchführung der vorstehend genannten Reaktionen. Bevorzugt sind insbesondere asymmetrische Hydroborierungen, asymmetrischenIf the catalysts contain transition metal complexes which contain stereoisomerically enriched compounds of the formula (I), the catalysts are particularly suitable for carrying out the above-mentioned reactions asymmetrically. In particular, asymmetrical hydroboration, asymmetrical
Hydrogenierungen und asymmetrische allylische Substitutionen.Hydrogenations and asymmetric allylic substitutions.
Bevorzugte asymmetrische Hydrogenierungen sind beispielsweise Hydrogenierungen von prochiralen C=C-Bindungen wie zum Beispiel prochiralen Enaminen, Olefmen, Enolethem, C=O-Bindungen wie zum Beispiel prochiralen Ketonen und C=N-Preferred asymmetric hydrogenations are, for example, hydrogenations of prochiral C = C bonds such as, for example, prochiral enamines, olefins, enol ethers, C = O bonds such as, for example, prochiral ketones and C = N-
Bindungen wie zum Beispiel prochirale Iminen. Besonders bevorzugte asymmetrische Hydrogenierungen sind Hydrogemerungen von prochiralen C=C- Bindungen wie zum Beispiel prochiralen Enaminen, Olefmen, und C=N-Bindungen wie zum Beispiel prochirale Iminen.Bonds such as prochiral imines. Particularly preferred asymmetric hydrogenations are hydrogerminations of prochiral C = C bonds such as, for example, prochiral enamines, olefins, and C = N bonds, such as prochiral imines.
Von der Erfindung ist daher auch ein Verfahren zur Herstellung von stereoiso- merenangereicherten, bevorzugt enantiomerenangereicherten Verbindungen umfasst, das dadurch gekennzeichnet ist, dass die von stereoisomerenangereicherten, bevorzugt enantiomerenangereicherten Verbindungen entweder durch katalytische Hydrierung von Olefmen, Enaminen, Enamiden, Iminen oder Ketonen oder durchThe invention therefore also encompasses a process for the preparation of stereoisomerically enriched, preferably enantiomerically enriched compounds, which is characterized in that the compounds which are stereoisomerically enriched, preferably enantiomerically enriched, either by catalytic hydrogenation of olefms, enamines, enamides, imines or ketones or by
Hydroborierung von Alkenen und gegebenenfalls anschließende Oxidation oder durch allylische Substitution erhalten werden und als Katalysatoren solche verwendet werden, die Ubergangsmetallkomplexe von stereoisomerenangereicherten Verbindungen der Formel (I) mit der dort angegebenen Bedeutung enthalten.Hydroboration of alkenes and, if appropriate, subsequent oxidation or are obtained by allylic substitution and the catalysts used are those which contain transition metal complexes of stereoisomerically enriched compounds of the formula (I) with the meaning given there.
Die Menge der eingesetzten Übergangsmetallverbindung oder des eingesetztenThe amount of transition metal compound used or the amount used
Übergangsmetallkomplexes kann bezogen auf den Metallgehalt beispielsweise 0.001 bis 5 mol.-% bezogen auf das eingesetzte Substrat betragen, bevorzugt sind 0.001 bis 0,5 mol.-%, ganz besonders bevorzugt 0.001 bis 0,1 mol.-%.The transition metal complex can be, for example, 0.001 to 5 mol%, based on the metal content, based on the substrate used, preferably 0.001 to 0.5 mol%, very particularly preferably 0.001 to 0.1 mol%.
In einer bevorzugten Ausführungsform können asymmetrische Hydrogenierungen, asymmetrische Hydroborierungen beispielsweise so durchgeführt werden, dass der Katalysator aus einer Übergangsmetallverbindung und einer stereoisomerenangereicherten Verbindung der Formel (I) gegebenenfalls in einem geeigneten Lösungsmittel erzeugt wird, das Substrat zugegeben wird und die Reaktionsmischung bei Reaktionstemperatur unter Wasserstoffdruck gesetzt werden bzw. ein geeignetesIn a preferred embodiment, asymmetric hydrogenation, asymmetric hydroboration can be carried out, for example, in such a way that the catalyst is optionally produced from a transition metal compound and a stereoisomerically enriched compound of the formula (I) in a suitable solvent, the substrate is added and the reaction mixture is placed under hydrogen pressure at the reaction temperature become or a suitable one
Boran zugesetzt wird.Borane is added.
In einer bevorzugten Ausiuhrungsform können asymmetrische allylische Substitutionen beispielsweise so durchgeführt werden, dass der Katalysator aus einer Ubergangsmetallverbindung und einer stereoisomerenangereicherten Verbindung derIn a preferred embodiment, asymmetric allylic substitutions can be carried out, for example, in such a way that the catalyst consists of a transition metal compound and a stereoisomerically enriched compound of
Formel (I) gegebenenfalls in einem geeigneten Lösungsmittel erzeugt wird und das Substrat und das Nukleophil zugegeben wird.Formula (I) is optionally generated in a suitable solvent and the substrate and the nucleophile are added.
Für Hydrogenierungen und Hydroborierungen werden vorzugsweise Katalysatoren eingesetzt, die Iridium- von Verbindungen der Formel (I) enthalten und für allylischeFor hydrogenation and hydroboration, catalysts are preferably used which contain iridium compounds of the formula (I) and for allylic ones
Substitutionen werden vorzugsweise Katalysatoren eingesetzt, die Palladiumkomplexe von Verbindungen der Formel (I) enthalten.Substitutions are preferably used catalysts which contain palladium complexes of compounds of formula (I).
Die für die einsetzbaren Übergangsmetallverbindungen oder Übergangsmetall- komplexe vorstehend beschriebenen Vorzugsbereiche gelten hierbei in analogerThe preferred ranges described above for the transition metal compounds or transition metal complexes that can be used apply here in an analogous manner
Weise. Die erfindungsgemäßen Katalysatoren eignen sich insbesondere in einem Verfahren zur Herstellung von stereoisomerenangereicherten, bevorzugt enantiomerenangereicherten Wirkstoffen von Arzneimitteln und Agrochemikalien, oder Zwischen- produkten dieser beiden Klassen.Wise. The catalysts of the invention are particularly suitable in a process for the preparation of stereoisomerically enriched, preferably enantiomerically enriched, active ingredients of medicaments and agricultural chemicals, or intermediates of these two classes.
Der Vorteil der vorliegenden Erfindung ist, dass die Liganden in effizienter Weise hergestellt werden können und ihre elektronischen und sterischen Eigenschaften ausgehend von einfach verfügbaren Edukten in einem weiten Bereich variabel sind. ' Weiterhin zeigen die erfindungsgemäßen Liganden und deren Ubergangsmetallkomplexe insbesondere in asymmetrischen Hydrogenierungen, Hydroborierungen und allylischen Substitutionen gute Enantioselektivitäten und Umsatzraten. The advantage of the present invention is that the ligands can be produced in an efficient manner and their electronic and steric properties are variable over a wide range starting from readily available starting materials. 'Furthermore, according to the invention show ligands and their transition metal complexes, especially in asymmetric hydrogenations, allylic substitutions hydroboration and good enantioselectivity and conversion rates.
BeispieleExamples
Beispiel 1example 1
Herstellung von (lR,4R)-l,7,7-Trimethylbicyclo[2.2.1]hept-2-en-2-yl-trifluor- methansulfonatPreparation of (IR, 4R) -1,7,7-trimethylbicyclo [2.2.1] hept-2-en-2-yl-trifluoromethanesulfonate
Ein Lösung von (li?,4i?)-l,7,7-Trimethylbicyclo[2.2.1]heptan-2-on {(D)-Kampfer} (10 mmol, 1.52 g) in THF (10 mL) wurde bei -78°C zu einer Lösung von Lithium- diisopropylamid (LDA, 10 mmol) in THF (25 mL) gegeben und für eine Stunde gerührt. Anschließend wurde eine Lösung von N-Phenyltrifluormethansulfonimid (10.7 mmol, 3.82 g) in THF (15 mL) zugegeben und die resultierende Reaktionsmischung bei 0°C für 14 Stunden gerührt. Zu dieser Reaktionsmischung wurden dann zunächst 30 mL gesättigte Ammoniumchlorid-Lösung und dann Di- ethylether zur Extraktion zugegeben. Die organische Phase wurde mit Wasser, undA solution of (li?, 4i?) - l, 7,7-trimethylbicyclo [2.2.1] heptan-2-one {(D) camphor} (10 mmol, 1.52 g) in THF (10 mL) was added -78 ° C to a solution of lithium diisopropylamide (LDA, 10 mmol) in THF (25 mL) and stirred for one hour. A solution of N-phenyltrifluoromethanesulfonimide (10.7 mmol, 3.82 g) in THF (15 mL) was then added and the resulting reaction mixture was stirred at 0 ° C. for 14 hours. 30 ml of saturated ammonium chloride solution and then diethyl ether were then added to this reaction mixture for extraction. The organic phase was washed with water, and
Kochsalz-Lösung gewaschen und über MgSO4 getrocknet. Der Rückstand wurde chromatographisch über Silicagel mit Pentan als Laufmittel gereinigt und ergab das gewünschte Produkt (2.70 g, 90 % d. Th.) in Form einer farblosen Flüssigkeit. [α]23 D = + 8.63 (c 1.07, CHC13) 13C ΝMR (75 MHz, CDCI3): δ 155.6, 118.9 (q, J= 318 Hz), 57.3, 54.2, 50.5, 31.2,Washed saline solution and dried over MgSO 4 . The residue was purified chromatographically on silica gel with pentane as the eluent and gave the desired product (2.70 g, 90% of theory) in the form of a colorless liquid. [α] 23 D = + 8.63 (c 1.07, CHC1 3 ) 13 C ΝMR (75 MHz, CDCI 3 ): δ 155.6, 118.9 (q, J = 318 Hz), 57.3, 54.2, 50.5, 31.2,
25.7, 20.0, 19.3, 9.8 ppm. MS (EI, 70 ev): 284 (M+, 22), 151 (20), 123 (100), 95 (38), 81 (31), 55 (24).25.7, 20.0, 19.3, 9.8 ppm. MS (EI, 70 ev): 284 (M + , 22), 151 (20), 123 (100), 95 (38), 81 (31), 55 (24).
Beispiel 2Example 2
Herstellung von (lR,5S)-6,6-DimethyIbicy clo [3.1.1] hept-2-en-2-yl-trifluor- methansulfonatPreparation of (IR, 5S) -6,6-dimethylcyclo [3.1.1] hept-2-en-2-yl-trifluoromethanesulfonate
Analog zu Beispiel 1 wurde vorstehend genanntes Produkt ausgehend von (IR,5S)~ 6,6-Dimethylbicyclo[3.1.1]heptan-2-on in einer Ausbeute von 92 % d. Th. erhalten.Analogously to Example 1, the product mentioned above was started from (IR, 5S) ~ 6,6-dimethylbicyclo [3.1.1] heptan-2-one in a yield of 92% of theory. Th. Received.
[α]26 D = -23.5 (c 0.545, CHC13). 13C NMR (75 MHz, CDC13): δ 155.4, 118.9 (q, J= 315 Hz), 111.8, 46.7, 40.5, 40.1,[α] 26 D = -23.5 (c 0.545, CHC1 3 ). 13 C NMR (75 MHz, CDC1 3 ): δ 155.4, 118.9 (q, J = 315 Hz), 111.8, 46.7, 40.5, 40.1,
32.1, 28.6, 25.9, 21.2 ppm.32.1, 28.6, 25.9, 21.2 ppm.
Beispiele 3 bis 9Examples 3 to 9
Herstellung von Azoarylverbin düngen der Formeln (IVa) und (IVb):Production of azoarylverbin fertilize the formulas (IVa) and (IVb):
Beispiel 3:Example 3:
Herstellung von 2-[(lR,4R)-l,7,7-Trimetlιylbicyclo[2.2.1]hept-2-en-2-yI]pyridinPreparation of 2 - [(IR, 4R) -l, 7,7-trimethyllicyclo [2.2.1] hept-2-en-2-yI] pyridine
Zu einer Lösung von n-BuLi (1.5 M in Hexan, 20 mmol, 14 mL) wurde bei -78°C tropfenweise eine Lösung von 2-Brompyridin (20 mmol, 3.16 g) in THF (20 mL) zugegeben. Die Reaktionsmischung wurde für 30 min bei -78°C gerührt und anschlie- ßend tropfenweise mit einer Lösung von ZnBr2 (1.7 M in THF, 21 mmol, 13 mL) versetzt. Nach weiteren 15 min bei -78°C, wurde die Lösung erwärmen gelassen und nach 30 min mit dem Alkenyltriflat aus Beispiel 1 (10 mmol, 2.84 g), Pd(dba)2 (2 mol.-%, 0.2 mmol, 0.12 g) und Diphenylphosphinoferrocen (dppf) (2 mol.-%, 0.2 mmol, 0.11 g) in THF (15 mL) versetzt. Die resultierende Mischung wurde an- schließend für 15 Stunden unter Rückfluss erhitzt. Das THF wurde im Vakuum entfernt und der Rückstand mit Diethylether verdünnt. Nach Waschen mit Wasser und Kochsalzlösung, wurde die organische Phase über MgSO4 getrocknet und im Vakuum eingeengt. Der ölige Rückstand wurde chromatographisch über Sihcagel mit Diethylether als Laufmittel gereinigt und ergab das gewünschte Produkt (1.66 g, 78 % d. Th.).A solution of 2-bromopyridine (20 mmol, 3.16 g) in THF (20 mL) was added dropwise to a solution of n-BuLi (1.5 M in hexane, 20 mmol, 14 mL) at -78 ° C. The reaction mixture was stirred for 30 min at -78 ° C and then a solution of ZnBr 2 (1.7 M in THF, 21 mmol, 13 mL) was added dropwise. After a further 15 min at -78 ° C, the solution was allowed to warm and after 30 min with the alkenyl triflate from Example 1 (10 mmol, 2.84 g), Pd (dba) 2 (2 mol%, 0.2 mmol, 0.12 g) ) and diphenylphosphinoferrocene (dppf) (2 mol%, 0.2 mmol, 0.11 g) in THF (15 mL). The resulting mixture was then refluxed for 15 hours. The THF was removed in vacuo and the residue was diluted with diethyl ether. After washing with water and brine, the organic phase was dried over MgSO 4 and concentrated in vacuo. The oily residue was purified by chromatography on SiCagel with diethyl ether as the eluent and gave the desired product (1.66 g, 78% of theory).
[α]27 D = -176.4 (c 1.825, CHC13).[α] 27 D = -176.4 (c 1.825, CHC1 3 ).
13C NMR (75 MHz, CDC13): δ 157.8, 149.8, 149.4, 136.1, 135.9, 121.5, 121.3, 57.3, 13 C NMR (75 MHz, CDC1 3 ): δ 157.8, 149.8, 149.4, 136.1, 135.9, 121.5, 121.3, 57.3,
55.3,55.3,
52.2, 32.1, 26.0, 20.1, 20.0, 14.5, 12.8 ppm, Beispiel 452.2, 32.1, 26.0, 20.1, 20.0, 14.5, 12.8 ppm, Example 4
Herstellung von 2-Brom-6-[(lR,4R)-l,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yI]- pyridinPreparation of 2-bromo-6 - [(IR, 4R) -1,7,7-trimethylbicyclo [2.2.1] hept-2-en-2-yI] pyridine
Analog zu Beispiel 3 wurde vorstehend genanntes Produkt ausgehend von 2,6-Di- brompyridin in einer Ausbeute von 70 % d. Th. erhalten.Analogously to Example 3, the product mentioned above was started from 2,6-disbromopyridine in a yield of 70% of theory. Th. Received.
13C NMR (75 MHz, CDC13): δ 158.6, 148.3, 141.6, 138.3, 137.7, 125.2, 119.7, 57.3, 55.2, 52.2, 31.9, 26.0, 20.0, 19.9, 12.7 ppm. 13 C NMR (75 MHz, CDC1 3 ): δ 158.6, 148.3, 141.6, 138.3, 137.7, 125.2, 119.7, 57.3, 55.2, 52.2, 31.9, 26.0, 20.0, 19.9, 12.7 ppm.
Beispiel 5Example 5
Herstellung von 2-[(lR,4R)-l,7,7-Trimethylbicyclo[2.2.1]hept-2-en-2-yl]chinolinPreparation of 2 - [(IR, 4R) -1, 7,7-trimethylbicyclo [2.2.1] hept-2-en-2-yl] quinoline
Analog zu Beispiel 3 wurde vorstehend genanntes Produkt ausgehend von 2-Analogously to Example 3, the product mentioned above was started from 2-
Bromchinolin in einer Ausbeute von 65 % d. Th. erhalten.Bromoquinoline in a yield of 65% of theory Th. Received.
[α]23 D = -181.3 (c 0.45, CHC13).[α] 23 D = -181.3 (c 0.45, CHC1 3 ).
Mp: 96-98°C 13C NMR (75 MHz, CDG ): δ 157.5, 150.1, 148.3, 137.8, 135.6, 130.0, 129.4,Mp: 96-98 ° C 13 C NMR (75 MHz, CDG): δ 157.5, 150.1, 148.3, 137.8, 135.6, 130.0, 129.4,
127.6, 127.0, 125.9, 120.2, 57.1, 55.7, 52.5, 32.1, 26.2, 20.2, 19.9, 13.1 ppm. .127.6, 127.0, 125.9, 120.2, 57.1, 55.7, 52.5, 32.1, 26.2, 20.2, 19.9, 13.1 ppm. ,
MS (EI, 70 ev): 263 (M+, 70), 248 (100), 220 (62).MS (EI, 70 ev): 263 (M + , 70), 248 (100), 220 (62).
Beispiel 6Example 6
Herstellung von 2-[(lR.5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl]pyridinPreparation of 2 - [(IR.5S) -6,6-dimethylbicyclo [3.1.1] hept-2-en-2-yl] pyridine
Analog zu Beispiel 3 wurde vorstehend genanntes Produkt ausgehend von 2- Brompyridin und dem Vinyltriflat aus Beispiel 2 in einer Ausbeute von 85 % d. Th. erhalten.Analogously to Example 3, the product mentioned above was started from 2-bromopyridine and the vinyl triflate from Example 2 in a yield of 85% of theory. Th. Received.
[α] 3 D = +27 (c 0.725, CHCI3). 13C NMR (75 MHz, CDC13): δ 158.2, 149.4, 147.8, 136.4, 124.5, 121.6, 119.3, 43.2,[α] 3 D = +27 (c 0.725, CHCI3). 13 C NMR (75 MHz, CDC1 3 ): δ 158.2, 149.4, 147.8, 136.4, 124.5, 121.6, 119.3, 43.2,
41.1, 38.2, 32.4, 31.9, 26.6, 21.3 ppm.41.1, 38.2, 32.4, 31.9, 26.6, 21.3 ppm.
MS (EI, 70 ev): 198 (M+, 47), 184 (100), 156 (14).MS (EI, 70 ev): 198 (M + , 47), 184 (100), 156 (14).
Beispiel 7Example 7
Herstellung von 2-Br om-6- [(lR.5S)-6,6-dimethylbicy clo [3.1.1] hept-2-en-2-yl] - pyridinPreparation of 2-Br om-6- [(IR.5S) -6,6-dimethylbicyclo [3.1.1] hept-2-en-2-yl] pyridine
Analog zu Beispiel 3 wurde vorstehend genanntes Produkt ausgehend von 2,6-Analogously to Example 3, the product mentioned above was started from 2,6-
Dibrompyridin und dem Vinyltriflat aus Beispiel 2 in einer Ausbeute von 70 % d. Th. erhalten.Dibromopyridine and the vinyl triflate from Example 2 in a yield of 70% of theory. Th. Received.
13C NMR (75 MHz, CDC13): δ 159.2, 146.3, 142.1, 138.8, 126.5, 125.7, 117.6, 42.9, 13 C NMR (75 MHz, CDC1 3 ): δ 159.2, 146.3, 142.1, 138.8, 126.5, 125.7, 117.6, 42.9,
40.9, 38.3, 32.5, 31.9, 26.6, 21.4 ppm. MS (EI, 70 ev): 278 (M++l, 70), 236 (100), 154 (46).40.9, 38.3, 32.5, 31.9, 26.6, 21.4 ppm. MS (EI, 70 ev): 278 (M + +1, 70), 236 (100), 154 (46).
Beispiel 8Example 8
Herstellung von 2-PhenyI-6-[(lR,4R)-l,7,7-trimethylbicyclo[2.2.1]hept-2-en-2- yTjpyridinPreparation of 2-phenyl-6 - [(IR, 4R) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-en-2-y-pyridine
Eine Lösung der Verbindung aus Beispiel 4 (0.50 mmol, 142 mg) und Pd(PPh3)4 (0.02 mmol, 23 mg, 4 mol.-%) in Toluol (2 mL) wurde mit einer Lösung von Na2CO3 (1 mmol, 106 mg) in H2O (1 mL) und anschließend mit einer Lösung von PhB(OH)2 , (0.53 mmol, 64 mg) in MeOH (1 mL) versetzt. Die Mischung wurde bei 85°C für 16A solution of the compound from Example 4 (0.50 mmol, 142 mg) and Pd (PPh 3 ) 4 (0.02 mmol, 23 mg, 4 mol%) in toluene (2 mL) was mixed with a solution of Na 2 CO 3 ( 1 mmol, 106 mg) in H 2 O (1 mL) and then a solution of PhB (OH) 2 , (0.53 mmol, 64 mg) in MeOH (1 mL) was added. The mixture was kept at 85 ° C for 16
Stunden gerührt. Nach Abkühlen wurde gesättigte, wässrige Ammoniaklösung (0.25 mL) und eine gesättigte Lösung von Na2CO3 (2.5 mL) zugegeben und die Mischung mit CH2C12 extrahiert. Die vereinigten organischen Phasen wurden mit Wasser und Kochsalzlösung gewaschen, über MgSO4 getrocknet und im Vakuum eingeengt. Der Rückstand wurde chromatographisch über Sihcagel mit 2 % Diethylether in Pentan als Laufmittel gereinigt und ergab das gewünschte Produkt (131 mg, 91 % d. Th.). [α]2α D = +166.5 (c 0.585, CHC13).Hours stirred. After cooling, saturated aqueous ammonia solution (0.25 mL) and a saturated solution of Na 2 CO 3 (2.5 mL) were added and the mixture was extracted with CH 2 C1 2 . The combined organic phases were washed with water and brine, dried over MgSO 4 and concentrated in vacuo. The residue was purified by chromatography on SiCagel with 2% diethyl ether in pentane as the eluent and gave the desired product (131 mg, 91% of theory). [α] 2α D = +166.5 (c 0.585, CHC1 3 ).
13C NMR (75 MHz, CDC13): δ 156.3, 154.7, 148.6, 138.8, 135.5, 127.6, 127.5, 13 C NMR (75 MHz, CDC1 3 ): δ 156.3, 154.7, 148.6, 138.8, 135.5, 127.6, 127.5,
125.8, 118.3, 116.1, 55.7, 54.1, 50.9, 30.7, 24.8, 18.7, 18.5, 11.7 ppm.125.8, 118.3, 116.1, 55.7, 54.1, 50.9, 30.7, 24.8, 18.7, 18.5, 11.7 ppm.
Beispiel 9Example 9
Herstellung von 2-[(lR,5S)-6.6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl]-6-phenyl- pyridinPreparation of 2 - [(IR, 5S) -6.6-dimethylbicyclo [3.1.1] hept-2-en-2-yl] -6-phenylpyridine
Analog zu Beispiel 8 wurde vorstehend genanntes Produkt ausgehend von derAnalogously to Example 8, the product mentioned above was started from the
Verbindung aus Beispiel 7 in einer Ausbeute von 95 % d. Th. erhalten. [α]25 D= -13.2 (c 0.56, CHC13).Compound from Example 7 in a yield of 95% of theory. Th. Received. [α] 25 D = -13.2 (c 0.56, CHC1 3 ).
13C NMR (75 MHz, CDC13): δ 157.5, 156.4, 147.9, 140.2, 137.1, 129.0, 128.9, 127.3, 124.4, 118.1, 117.3, 43.0, 41.1, 38.3, 32.5, 31.9, 26.8, 21.4 ppm. MS (EI, 70 ev): 275 (M+, 100), 260 (78), 232 (85). 13 C NMR (75 MHz, CDC1 3 ): δ 157.5, 156.4, 147.9, 140.2, 137.1, 129.0, 128.9, 127.3, 124.4, 118.1, 117.3, 43.0, 41.1, 38.3, 32.5, 31.9, 26.8, 21.4 ppm. MS (EI, 70 ev): 275 (M + , 100), 260 (78), 232 (85).
Beispiele 10 bis 15Examples 10 to 15
Herstellung von Nerbindungen der Formeln (Nlla) und (Nπb):Production of Nerbundungen of the formulas (Nlla) and (Nπb):
Beispiel 10Example 10
Herstellung von 2- [(lS,2S,3R,4S)-3-(Diphenylphosphoryl)-l ,7,7-trimethyIbi- cyclo[2.2.1]hept-2-yI]pyridinPreparation of 2- [(IS, 2S, 3R, 4S) -3- (diphenylphosphoryl) -1,7,7-trimethyIcycloc [2.2.1] hept-2-yI] pyridine
Zu einer Lösung von Kalium-tert.-butoxid (0.20 mmol, 23 mg) in 1 mL DMSO wurden unter Argon nacheinander Diphenylphosphinoxid (1 mmol, 202 mg) in 2 mL DMSO und die Verbindung aus Beispiel 3 (1 mmol, 213 mg) zugegeben. Die Reaktionsmischung wurde bei 60°C für 15 Stunden gerührt. Nach Abkühlen auf Raum- temperatur wurden Wasser und CH2C12 zugegeben, die vereinigten organischenDiphenylphosphine oxide (1 mmol, 202 mg) in 2 mL DMSO and the compound from Example 3 (1 mmol, 213 mg) were added to a solution of potassium tert-butoxide (0.20 mmol, 23 mg) in 1 mL DMSO under argon. added. The reaction mixture was stirred at 60 ° C for 15 hours. After cooling to room temperature, water and CH 2 C1 2 were added, the combined organic
Phasen mit Wasser und Kochsalzlösung gewaschen, über MgSO getrocknet und im Vakuum eingeengt. Der Rückstand wurde chromatographisch über Sihcagel mit 10 % Diethylether in CH2C12 als Laufmittel gereinigt und ergab das gewünschte Produkt (361 mg, 87 % d. Th.). [α]23 D = +78.9 (c 0.56, CHC13). Mp: 132-139°CPhases washed with water and brine, dried over MgSO 4 and in Vacuum concentrated. The residue was purified by chromatography over SiHcagel with 10% diethyl ether in CH 2 C1 2 as the eluent and gave the desired product (361 mg, 87% of theory). [α] 23 D = +78.9 (c 0.56, CHC1 3 ). Mp: 132-139 ° C
13C NMR (75 MHz, CDCI3): δ 159.7, 134.7 (d, J= 94.0 Hz), 133.4 (d, J= 94.0 Hz), 131.6-131.3 (m), 130.7 (d, J = 2.7 Hz), 128.9 (d, J = 11.0 Hz), 127.7 (d, J = 11.0 Hz), 125.6, 121.4, 53.3 (d, J= 2.9 Hz), 52.2 (d, J= 5.1 Hz), 51.0, 48.1, 45.2 (d, J = 70.4 Hz), 32.3 (d, J= 13.7 Hz), 28.2, 21.2, 20.2, 14.5 ppm. 31P NMR (81 MHz, CDC13): δ 32.8 ppm. 13 C NMR (75 MHz, CDCI 3 ): δ 159.7, 134.7 (d, J = 94.0 Hz), 133.4 (d, J = 94.0 Hz), 131.6-131.3 (m), 130.7 (d, J = 2.7 Hz) , 128.9 (d, J = 11.0 Hz), 127.7 (d, J = 11.0 Hz), 125.6, 121.4, 53.3 (d, J = 2.9 Hz), 52.2 (d, J = 5.1 Hz), 51.0, 48.1, 45.2 (d, J = 70.4 Hz), 32.3 (d, J = 13.7 Hz), 28.2, 21.2, 20.2, 14.5 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 32.8 ppm.
MS (EI, 70 ev): 415 (M+, 6), 332 (30), 214 (100).MS (EI, 70 ev): 415 (M + , 6), 332 (30), 214 (100).
Beispiel 11Example 11
Herstellung von 2-[(lS,2R,3S,4S)-3-(Diphenylphosphoryl)-l,7,7-trimethylbi- cy clo [2.2.1] hept-2-yl] -6-phenylpyridinPreparation of 2 - [(IS, 2R, 3S, 4S) -3- (diphenylphosphoryl) -1,7,7-trimethylbicyclo [2.2.1] hept-2-yl] -6-phenylpyridine
Analog zu Beispiel 10 wurde vorstehend genanntes Produkt ausgehend von derAnalogously to Example 10, the product mentioned above was started from the
Verbindung aus Beispiel 8 mit Diphenylphosphinoxid in einer Ausbeute von 72 % d. Th. erhalten.Compound from Example 8 with diphenylphosphine oxide in a yield of 72% of theory. Th. Received.
[α]22 D = -68.9 (c 0.505, CHCI3).[α] 22 D = -68.9 (c 0.505, CHCI3).
Mp: 69-72°CMp: 69-72 ° C
13C NMR (75 MHz, CDC13): δ 159.2, 155.2, 140.0, 136.4, 135.5, 134.2, 133.8, 13 C NMR (75 MHz, CDC1 3 ): δ 159.2, 155.2, 140.0, 136.4, 135.5, 134.2, 133.8,
132.6, 131.6-131.4 (m), 130.7 (d, J= 2.3 Hz), 129.1, 128.8 (d, J = 11.0 Hz), 127.6 (d, J= 11.0 Hz), 126.9, 124.0, 117.8, 53.6 (d, J= 2.9 Hz), 52.1 (d, J= 5.2 Hz), 51.1,132.6, 131.6-131.4 (m), 130.7 (d, J = 2.3 Hz), 129.1, 128.8 (d, J = 11.0 Hz), 127.6 (d, J = 11.0 Hz), 126.9, 124.0, 117.8, 53.6 (d , J = 2.9 Hz), 52.1 (d, J = 5.2 Hz), 51.1,
48.1, 45.9, 45.0, 32.6 (d, J= 13.7 Hz), 28.4, 21.1, 20.2, 14.6 ppm.48.1, 45.9, 45.0, 32.6 (d, J = 13.7 Hz), 28.4, 21.1, 20.2, 14.6 ppm.
31P NMR (81 MHz, CDC13): δ 32.6 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 32.6 ppm.
MS (EI, 70 ev): 477 (M+, 7), 276 (100). Beispiel 12MS (EI, 70 ev): 477 (M + , 7), 276 (100). Example 12
Herstellung von 2-[(lS,2S,3R,4S)-3-(DicyclohexylphosphoryI)-l,7,7-trimethylbi- cy clo [2.2.1 ] hept-2-yi] pyridinPreparation of 2 - [(IS, 2S, 3R, 4S) -3- (dicyclohexylphosphoryl) -1, 7,7-trimethylbicyclo [2.2.1] hept-2-yi] pyridine
Analog zu Beispiel 10 wurde vorstehend genanntes Produkt ausgehend von der Verbindung aus Beispiel 8 mit Dicyclohexylphosphmoxid in einer Ausbeute von 55 % d. Th. erhalten. [ ]27 D = +14.7 (c 0.475, CHC13). Mp: .128-132°CAnalogously to Example 10, the product mentioned above was started from the compound from Example 8 with dicyclohexylphosphmoxide in a yield of 55% of theory. Th. Received. [] 27 D = +14.7 (c 0.475, CHC1 3 ). Mp: .128-132 ° C
13C NMR (75 MHz, CDC13): δ 160.3, 148.9, 135.9, 126.1, 121,8, 53.3 (d, J = 3.9 Hz), 51.7 (d, J= 5.0 Hz), 50.6, 48.3 (d, J= 2.1 Hz), 41.5-38.2 (m), 32.2 (d, J= 11.8 Hz), 28.2-26.4 (m), 21.4, 20.1, 14.6 ppm. 31P NMR (81 MHz, CDC13): δ 50.8 ppm. MS (EI, 70 ev): 427 (M+, 2.5), 344 (17), 214 (100). 13 C NMR (75 MHz, CDC1 3 ): δ 160.3, 148.9, 135.9, 126.1, 121.8, 53.3 (d, J = 3.9 Hz), 51.7 (d, J = 5.0 Hz), 50.6, 48.3 (d, J = 2.1 Hz), 41.5-38.2 (m), 32.2 (d, J = 11.8 Hz), 28.2-26.4 (m), 21.4, 20.1, 14.6 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 50.8 ppm. MS (EI, 70 ev): 427 (M + , 2.5), 344 (17), 214 (100).
Beispiel 13Example 13
Herstellung von 2-[(lS,2S,3R,4S)-3-(DiphenylphosphoryI)-l,7,7-trimethylbi- cyclo[2.2.1]hept-2-yl]chinolinPreparation of 2 - [(IS, 2S, 3R, 4S) -3- (diphenylphosphoryl) -1,7,7-trimethylcyclo [2.2.1] hept-2-yl] quinoline
Analog zu Beispiel 10 wurde vorstehend genanntes Produkt ausgehend von der Verbindung aus Beispiel 5 mit Diphenylphosphinoxid in einer Ausbeute von 93 % d. Th. erhalten. [α]28 D = +83.4 (c 0.525, CHCI3).Analogously to Example 10, the product mentioned above was started from the compound from Example 5 with diphenylphosphine oxide in a yield of 93% of theory. Th. Received. [α] 28 D = +83.4 (c 0.525, CHCI 3 ).
Mp: 70-78°CMp: 70-78 ° C
13C NMR (75 MHz, CDC13): δ 160.1, 147.5, 135.1, 133.8, 132.5, 131.6-131.4 (m), 130.4 (d, J= 2.7 Hz), 129.6-128.8 (m), 127.6-127.2 (m), 125.9, 123.9, 54.2 (d, J=2.4 Hz), 52.7 (d, J = 4.6 Hz), 51.3, 48.0, 45.0 (d, J = 80.0 Hz), 32.4 (d, J = 14.0 Hz), 28.3, 21.2, 20.2, 14.9 ppm. 31P NMR (81 MHz, CDC13): δ 32.9 ppm. 13 C NMR (75 MHz, CDC1 3 ): δ 160.1, 147.5, 135.1, 133.8, 132.5, 131.6-131.4 (m), 130.4 (d, J = 2.7 Hz), 129.6-128.8 (m), 127.6-127.2 ( m), 125.9, 123.9, 54.2 (d, J = 2.4 Hz), 52.7 (d, J = 4.6 Hz), 51.3, 48.0, 45.0 (d, J = 80.0 Hz), 32.4 (d, J = 14.0 Hz) , 28.3, 21.2, 20.2, 14.9 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 32.9 ppm.
MS (EI, 70 ev): 465 (M+, 3), 382 (7), 264 (100).MS (EI, 70 ev): 465 (M + , 3), 382 (7), 264 (100).
Beispiel 14Example 14
Herstellung von 2-[(lS,2R,3S,5R)-3-(Diphenylphosphoryl)-6,6-dimethylbi- cyclo[3.1.1]hept-2-yl]pyridinPreparation of 2 - [(IS, 2R, 3S, 5R) -3- (diphenylphosphoryl) -6,6-dimethylbicyclo [3.1.1] hept-2-yl] pyridine
Analog zu Beispiel 10 wurde vorstehend genanntes Produkt ausgehend von der Ver- bindung aus Beispiel 6 mit Diphenylphosphinoxid in einer Ausbeute von 86 % d. Th. erhalten.Analogously to Example 10, the product mentioned above was started with the compound from Example 6 with diphenylphosphine oxide in a yield of 86% of theory. Th. Received.
[α]26 D = -24 (c 0.56, CHC13).[α] 26 D = -24 (c 0.56, CHC1 3 ).
Mp: 57-63 °CMp: 57-63 ° C
13C NMR (75 MHz, CDC13): δ 162.'6 (d, J= 2.7 Hz), 147.24, 135.9, 134.3, 133.1 (d, J- 14 Hz), 131.8, 131.6 (m), 131.0 (d, J= 2.7 Hz), 128.9 (d, J= 11.0 Hz), 127.6 (d, 13 C NMR (75 MHz, CDC1 3 ): δ 162. ' 6 (d, J = 2.7 Hz), 147.24, 135.9, 134.3, 133.1 (d, J- 14 Hz), 131.8, 131.6 (m), 131.0 ( d, J = 2.7 Hz), 128.9 (d, J = 11.0 Hz), 127.6 (d,
.7= 11.0 Hz), 123.9, 121.0, 48.3 (d, J= 5.6 Hz), 46.6, 40.7 (d, J= 3.8 Hz), 39.1, 30.9, 27.9, 26.5 (d, J= 2.1 Hz), 25.6, 24.7, 22.7 ppm..7 = 11.0 Hz), 123.9, 121.0, 48.3 (d, J = 5.6 Hz), 46.6, 40.7 (d, J = 3.8 Hz), 39.1, 30.9, 27.9, 26.5 (d, J = 2.1 Hz), 25.6 , 24.7, 22.7 ppm.
31P NMR (81 MHz, CDC13): δ 38.4 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 38.4 ppm.
MS (EI, 70 ev): 401 (M+, 13), 200 (100).MS (EI, 70 ev): 401 (M + , 13), 200 (100).
Beispiel 15Example 15
Herstellung von 2-[(lS,2R,3S,5R)-3-(Diphenylphosphoryl)-6,6-dimethylbicyclo- [3.1.1]hept-2-yl]-6-phenyl-pyridinPreparation of 2 - [(IS, 2R, 3S, 5R) -3- (diphenylphosphoryl) -6,6-dimethylbicyclo- [3.1.1] hept-2-yl] -6-phenylpyridine
Analog zu Beispiel 10 wurde vorstehend genanntes Produkt ausgehend von der Verbindung aus Beispiel 9 mit Diphenylphosphinoxid in einer Ausbeute von 78 % d. Th. erhalten.Analogously to Example 10, the product mentioned above was started with the compound from Example 9 with diphenylphosphine oxide in a yield of 78% of theory. Th. Received.
[α]29 D = +59.2 (c 0.76, CHC13). Mp: 67-73°C 13C NMR (75 MHz, CDC13): δ 162.6 (d, J = 2.3 Hz), 154.4, 140.2, 136.9, 134.4, 133.1 (d, J= 3.2 Hz), 131.8-131.5 (m), 130.9 (d, J= 2.7 Hz), 129.1 (d, J= 3.2 Hz), 128.9, 127.5 (d, 7= 11.3 Hz), 126.9, 122.4, 117.4, 48.3 (d, J= 5.8 Hz), 46.9, 40.9 (d, J= 4.1 Hz), 39.3, 31.4, 28.0, 26.6, 25.9, 24.9, 23.0 ppm. 31P NMR (81 MHz, CDC13): δ 37.9 ppm.[α] 29 D = +59.2 (c 0.76, CHC1 3 ). Mp: 67-73 ° C 13 C NMR (75 MHz, CDC1 3 ): δ 162.6 (d, J = 2.3 Hz), 154.4, 140.2, 136.9, 134.4, 133.1 (d, J = 3.2 Hz), 131.8-131.5 (m), 130.9 (d , J = 2.7 Hz), 129.1 (d, J = 3.2 Hz), 128.9, 127.5 (d, 7 = 11.3 Hz), 126.9, 122.4, 117.4, 48.3 (d, J = 5.8 Hz), 46.9, 40.9 (d , J = 4.1 Hz), 39.3, 31.4, 28.0, 26.6, 25.9, 24.9, 23.0 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 37.9 ppm.
MS (EL 70 ev): 477 (M+, 7), 276 (100).MS (EL 70 ev): 477 (M + , 7), 276 (100).
Beispiele 16-21Examples 16-21
Herstellung von Nerbindungen der Formeln (la) und (Ib):Production of compounds of the formulas (la) and (Ib):
Beispiel 16Example 16
Herstellung von 2- [(lS,2R,3R,4S)-3-(Diphenylphosphino)-l ,7,7-trimethylbicyclo- [2.2.1]hept-2-yl]pyridinPreparation of 2- [(IS, 2R, 3R, 4S) -3- (diphenylphosphino) -1,7,7-trimethylbicyclo- [2.2.1] hept-2-yl] pyridine
Ein Kolben wurde unter Argon mit der Verbindung aus Beispiel 12 (0.5 mmol, 208 mg), Toluol (15 mL), Trichlorsilan (10 equiv, 5 mmol, 0.5 mL) und Triethylamin (20 equiv, 10 mmol, 1.4 mL) beschickt und die Mischung für 16 Stunden auf 120°C erhitzt. Nach Abkühlen auf Raumtemperatur wurde Toluol und der Überschuss anA flask was charged with the compound from Example 12 (0.5 mmol, 208 mg), toluene (15 mL), trichlorosilane (10 equiv, 5 mmol, 0.5 mL) and triethylamine (20 equiv, 10 mmol, 1.4 mL) under argon and the mixture was heated to 120 ° C for 16 hours. After cooling to room temperature, toluene and the excess were on
Trichlorsilan im Vakuum abgezogen. Der Rückstand wurde in Toluol (15 mL) aufgenommen und vorsichtig mit entgaster, wässriger 10 % NaHC03-Lösung versetzt. Die Phasen wurden unter Argon getrennt, das Toluol abgezogen und der Rückstand mit Diethylether gewaschen. Nach Filtration und Trocknen im Vakuum wurde das Produkt als viskose Flüssigkeit erhalten (174 mg, 87 %).Trichlorosilane stripped off in vacuo. The residue was taken up in toluene (15 mL) and degassed, aqueous 10% NaHC0 3 solution was carefully added. The phases were separated under argon, the toluene was stripped off and the residue was washed with diethyl ether. After filtration and drying in vacuo, the product was obtained as a viscous liquid (174 mg, 87%).
13C NMR (75 MHz, CDCI3): δ 159.6, 147.0, 139.0 (d, J= 15 Hz), 136.3 (d, J= 15 Hz), 133.6, 133.4, 133.1, 131.5, 131.3, 128.0, 127.3-126.9 (m), 126.1 (d, /= 7.6 Hz), 124.3, 123.6, 119.3, 55.6 (d, J= 9.9 Hz), 50.4 (d, J= 3.9 Hz), 50.0, 48.1 (d, J= 12.5 Hz), 42.6 (d, J= 13.7 Hz), 29.9 (d, J= 7.3 Hz), 27.3, 20.0, 19.8 (d, J= 20.0 Hz), 13.4 ppm. 13 C NMR (75 MHz, CDCI 3 ): δ 159.6, 147.0, 139.0 (d, J = 15 Hz), 136.3 (d, J = 15 Hz), 133.6, 133.4, 133.1, 131.5, 131.3, 128.0, 127.3- 126.9 (m), 126.1 (d, / = 7.6 Hz), 124.3, 123.6, 119.3, 55.6 (d, J = 9.9 Hz), 50.4 (d, J = 3.9 Hz), 50.0, 48.1 (d, J = 12.5 Hz), 42.6 (d, J = 13.7 Hz), 29.9 (d, J = 7.3 Hz), 27.3, 20.0, 19.8 (d, J = 20.0 Hz), 13.4 ppm.
31P NMR (81 MHz, CDC13): δ -2.1 ppm. Beispiel 17 31 P NMR (81 MHz, CDC1 3 ): δ -2.1 ppm. Example 17
Herstellung von 2-[(lS,2R,3S,4S)-3-(Diphenylphosphino)-l,7,7-trimethylbicyclo- [2.2.1]hept-2-yl]-6-phenyl-pyridinPreparation of 2 - [(IS, 2R, 3S, 4S) -3- (diphenylphosphino) -1,7,7-trimethylbicyclo- [2.2.1] hept-2-yl] -6-phenyl-pyridine
Analog zu Beispiel 16 wurde vorstehend genanntes Produkt ausgehend von derAnalogously to Example 16, the product mentioned above was started from the
Verbindung aus Beispiel 11 in einer Ausbeute von 92 % d. Th. erhalten.Compound from Example 11 in a yield of 92% of theory Th. Received.
13C NMR (75 MHz, CDC13): δ 159.1, 153.7, 139.2 (d, J= 15 Hz), 138.9, 136.2 (d, J = 15 Hz), 134.5, 133.3 (d, J = 18.8 Hz), 131.4 (d, J = 18.8 Hz), 127.6-127.2 (m), 13 C NMR (75 MHz, CDC1 3 ): δ 159.1, 153.7, 139.2 (d, J = 15 Hz), 138.9, 136.2 (d, J = 15 Hz), 134.5, 133.3 (d, J = 18.8 Hz), 131.4 (d, J = 18.8 Hz), 127.6-127.2 (m),
126.8, 126.1 (d, J- 8.0 Hz) 125.6, 122.3, 115.7, 55.7 (d, J= 9.9 Hz), 50.4 (d, J= 4.1126.8, 126.1 (d, J- 8.0 Hz) 125.6, 122.3, 115.7, 55.7 (d, J = 9.9 Hz), 50.4 (d, J = 4.1
Hz), 50.3, 48.1 (d, J = 12.8 Hz), 42.4 (d, J = 13.4 Hz), 30.1 (d, J = 6.9 Hz), 27.4,Hz), 50.3, 48.1 (d, J = 12.8 Hz), 42.4 (d, J = 13.4 Hz), 30.1 (d, J = 6.9 Hz), 27.4,
19.9, 19.7, 13.5 ppm.19.9, 19.7, 13.5 ppm.
31P NMR (81 MHz, CDC13): δ -2.05 ppm. MS (EI, 70 ev): 475 (M+, 26), 392 (18), 290 (100), 182 (32). 31 P NMR (81 MHz, CDC1 3 ): δ -2.05 ppm. MS (EI, 70 ev): 475 (M + , 26), 392 (18), 290 (100), 182 (32).
Beispiel 18Example 18
Herstellung von 2-[(lS,2S,3R,4S)-3-(Dicyclohexylphosphoryl)-l ,7,7-trimethylbi- cyclo[2.2.1]hept-2-yl]py-ridinePreparation of 2 - [(IS, 2S, 3R, 4S) -3- (dicyclohexylphosphoryl) -1,7,7-trimethylbicyclo [2.2.1] hept-2-yl] py-ridine
Analog zu Beispiel 16 wurde vorstehend genanntes Produkt ausgehend von derAnalogously to Example 16, the product mentioned above was started from the
Verbindung aus Beispiel 12 in einer Ausbeute von 61 % d. Th. erhalten.Compound from Example 12 in a yield of 61% of theory Th. Received.
[α]27 D= +14.7 (c 0.475, CHC13). Mp: 128-132°C[α] 27 D = +14.7 (c 0.475, CHC1 3 ). Mp: 128-132 ° C
13C NMR (75 MHz, CDC13): δ 160.3, 148.9, 135.9, 126.1, 121,8, 53.3 (d, J = 3.9 13 C NMR (75 MHz, CDC1 3 ): δ 160.3, 148.9, 135.9, 126.1, 121.8, 53.3 (d, J = 3.9
Hz), 51.7 (d, J= 5.0 Hz), 50.6, 48.3 (d, J= 2.1 Hz), 41.5-38.2 (m), 32.2 (d, J= 11.8Hz), 51.7 (d, J = 5.0 Hz), 50.6, 48.3 (d, J = 2.1 Hz), 41.5-38.2 (m), 32.2 (d, J = 11.8
Hz), 28.2-26.4 (m), 21.4, 20.1, 14.6 ppm.Hz), 28.2-26.4 (m), 21.4, 20.1, 14.6 ppm.
31P NMR (81 MHz, CDC13): δ 50.8 ppm. MS (EI, 70 ev): 427 (M+, 2.5), 344 (17), 214 (100). Beispiel 19 31 P NMR (81 MHz, CDC1 3 ): δ 50.8 ppm. MS (EI, 70 ev): 427 (M + , 2.5), 344 (17), 214 (100). Example 19
Herstellung von 2-[(lS,2R,3S,4S)-3-(Diphenylphosphino)-l,7,7-trimethylbicyclo- [2.2.1]hept-2-yl]chinolinPreparation of 2 - [(IS, 2R, 3S, 4S) -3- (diphenylphosphino) -1, 7,7-trimethylbicyclo- [2.2.1] hept-2-yl] quinoline
Analog zu Beispiel 16 wurde vorstehend genanntes Produkt ausgehend von der Verbindung aus Beispiel 13 in einer Ausbeute von 60 % d. Th. erhalten. 13C NMR (75 MHz, CDC13): δ 160.1, 146.3, 139.2 (d, J = 15.0 Hz), 136.1 (d, J = 15.0 Hz), 133.5, 133.2, 133.1, 131.4 (d, J= 17.2 Hz), 128.3, 127.4-126.8 (m), 126.0- 125.4 (m), 124.2, 122.2, 56.4 (d, J= 10.1 Hz), 50.9 (d, J= 3.8 Hz), 50.5, 48.1 (d, J=Analogously to Example 16, the product mentioned above was started from the compound from Example 13 in a yield of 60% of theory. Th. Received. 13 C NMR (75 MHz, CDC1 3 ): δ 160.1, 146.3, 139.2 (d, J = 15.0 Hz), 136.1 (d, J = 15.0 Hz), 133.5, 133.2, 133.1, 131.4 (d, J = 17.2 Hz ), 128.3, 127.4-126.8 (m), 126.0-125.4 (m), 124.2, 122.2, 56.4 (d, J = 10.1 Hz), 50.9 (d, J = 3.8 Hz), 50.5, 48.1 (d, J =
12.8 Hz), 42.3 (d, J= 13.7 Hz), 30.0 (d, J= 7.4 Hz), 27.4, 20.0, 19.7, 13.7 ppm. 31P NMR (81 MHz, CDC13): δ -1.53 ppm. MS (EI, 70 ev): 449 (M1", 28), 366 (17), 264 (100), 156 (33).12.8 Hz), 42.3 (d, J = 13.7 Hz), 30.0 (d, J = 7.4 Hz), 27.4, 20.0, 19.7, 13.7 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ -1.53 ppm. MS (EI, 70 ev): 449 (M 1 " , 28), 366 (17), 264 (100), 156 (33).
Beispiel 20Example 20
Herstellung von 2-[(lS,2R,3S,5R)-3-(DiphenyIphosphino)-6,6-dimethylbicyclo- [3.1.1]hept-2-yl]pyridinPreparation of 2 - [(IS, 2R, 3S, 5R) -3- (diphenylphosphino) -6,6-dimethylbicyclo- [3.1.1] hept-2-yl] pyridine
Analog zu Beispiel 16 wurde vorstehend genanntes Produkt ausgehend von derAnalogously to Example 16, the product mentioned above was started from the
Verbindung aus Beispiel 14 in einer Ausbeute von 81 % d. Th. erhalten. 13C NMR (75 MHz, CDC13): δ 162.4 (d, J= 2.6 Hz), 146.2, 136.8 (d, J= 15.5 Hz), 136.2 (d, J= 15.5 Hz), 134.1, 133.3 (d, J= 18.7 Hz), 132.7 (d, J= 18.7 Hz), 127.6- 127.1 (m), 126.2 (d, J= 7.0 Hz), 122.0, 119.1, 50.7 (d, J= 2.6 Hz), 47.8 (d, J= 4.9 Hz), 40.6 (d, J= 2.3 Hz), 38.1 (d, J= 1.6 Hz), 30.4 (d, J= 17.8 Hz), 30.0, 26.5, 21.7,Compound from Example 14 in a yield of 81% of theory. Th. Received. 13 C NMR (75 MHz, CDC1 3 ): δ 162.4 (d, J = 2.6 Hz), 146.2, 136.8 (d, J = 15.5 Hz), 136.2 (d, J = 15.5 Hz), 134.1, 133.3 (d, J = 18.7 Hz), 132.7 (d, J = 18.7 Hz), 127.6- 127.1 (m), 126.2 (d, J = 7.0 Hz), 122.0, 119.1, 50.7 (d, J = 2.6 Hz), 47.8 (d , J = 4.9 Hz), 40.6 (d, J = 2.3 Hz), 38.1 (d, J = 1.6 Hz), 30.4 (d, J = 17.8 Hz), 30.0, 26.5, 21.7,
21.4 (d, J= 8.1 Hz) ppm. 31P NMR (81 MHz, CDC13): δ 10.5 ppm. MS (EI, 70 ev): 385 (M+, 6), 308 (48), 200 (100). Beispiel 2121.4 (d, J = 8.1 Hz) ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 10.5 ppm. MS (EI, 70 ev): 385 (M + , 6), 308 (48), 200 (100). Example 21
Herstellung von 2-[(lS,2R,3S,5R)-3-(Diphenylphosphmo)-6,6-dimethylbicyclo- [3.1.1] hept-2-yl] -6-phenyl-py ridinPreparation of 2 - [(IS, 2R, 3S, 5R) -3- (diphenylphosphmo) -6,6-dimethylbicyclo- [3.1.1] hept-2-yl] -6-phenylpyridine
Analog zu Beispiel 16 wurde vorstehend genanntes Produkt ausgehend von derAnalogously to Example 16, the product mentioned above was started from the
Verbindung aus Beispiel 15 in einer Ausbeute von 82 % d. Th. erhalten.Compound from Example 15 in a yield of 82% of theory. Th. Received.
13C NMR (75 MHz, CDC13): δ 161.9 (d, J= 2.3 Hz), 153.0, 138.9, 136.9 (d, J= 15.5 13 C NMR (75 MHz, CDC1 3 ): δ 161.9 (d, J = 2.3 Hz), 153.0, 138.9, 136.9 (d, J = 15.5
Hz), 136.1 (d, J = 15.5 Hz), 135.0, 133.2 (d, J = 18.8 Hz), 132.7 (d, J = 18.8 Hz), 127.6-127.2 (m), 126.1 (d, J = 7.4 Hz), 125.6, 120.5, 115.5, 50.7 (d, J= 19.0 Hz),Hz), 136.1 (d, J = 15.5 Hz), 135.0, 133.2 (d, J = 18.8 Hz), 132.7 (d, J = 18.8 Hz), 127.6-127.2 (m), 126.1 (d, J = 7.4 Hz ), 125.6, 120.5, 115.5, 50.7 (d, J = 19.0 Hz),
47.7 (d, J= 5.2 Hz), 40.7 (d, J= 2.5 Hz), 38.4, 30.6 (d, J= 18.5 Hz), 30.3, 26.6, 21.9,47.7 (d, J = 5.2 Hz), 40.7 (d, J = 2.5 Hz), 38.4, 30.6 (d, J = 18.5 Hz), 30.3, 26.6, 21.9,
21.4 (d, 7= 8.3 Hz) ppm.21.4 (d, 7 = 8.3 Hz) ppm.
31P NMR (81 MHz, CDC13): δ 10.1 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 10.1 ppm.
MS (EI, 70 ev): 461 (M+, 2), 384 (5), 276 (100).MS (EI, 70 ev): 461 (M + , 2), 384 (5), 276 (100).
Beispiele 22-27Examples 22-27
Herstellung von IridiumkomplexenManufacture of iridium complexes
Beispiel 22Example 22
[Ir(16)(cod)]BARF[Ir (16) (cod)] BARF
Ein Zweihalskolben mit Rückflusskühler wurde mit dem Liganden aus Beispiel 16 (0.1 mmol, 40 mg), [Ir(cod)Cl]2 (0.05 mmol, 33.6 mg) und CH2C12 (5 mL) beschickt.The ligand from Example 16 (0.1 mmol, 40 mg), [Ir (cod) Cl] 2 (0.05 mmol, 33.6 mg) and CH 2 C1 2 (5 mL) was charged to a two-necked flask with a reflux condenser.
Die Lösung wurde für eine Stunde unter Rückfluss erhitzt, bis das 31P NMR das Verschwinden des freien Liganden anzeigte. Nach Abkühlen auf Raumtemperatur wurden Na[BARF] (0.15 mmol, 130 mg) und H2O (5 mL) zugegeben und die resultierende zwei-phasige Reaktionsmischung für 30 min stark gerührt. Die Phasen wurden getrennt, die wässrige Phase mit CH2C12 (2 x 20 mL) extrahiert, die vereinigten organischen Phasen H2O (10 mL) gewaschen und im Vakuum eingeengt. Der Rückstand wurde säulenchromatographisch mit 50 % CH2C12 in Pentan als Laufmittel ) gereinigt und ergab den Iridium-Komplex als orangefarbenen Feststoff (88 %, 138 mg). Mp: 173-177°C 13C NMR (75 MHz, CDC13): δ 163.5-161.1 (m), 151.7, 139.7, 135.2, 134.6 (d, 7 =The solution was refluxed for one hour until 31 P NMR indicated the disappearance of the free ligand. After cooling to room temperature, Na [BARF] (0.15 mmol, 130 mg) and H 2 O (5 mL) were added and the resulting two-phase reaction mixture was stirred vigorously for 30 min. The phases were separated, the aqueous phase extracted with CH 2 C1 2 (2 x 20 mL), the combined organic phases H 2 O (10 mL) washed and concentrated in vacuo. The residue was purified by column chromatography with 50% CH 2 C1 2 in pentane as eluent) and gave the iridium complex as an orange solid (88%, 138 mg). Mp: 173-177 ° C 13 C NMR (75 MHz, CDC1 3 ): δ 163.5-161.1 (m), 151.7, 139.7, 135.2, 134.6 (d, 7 =
12.6 Hz), 133.6 (d, 7= 9.3 Hz), 132.1-122.8 (m), 119.5, 117.8, 93.7 (d, J= 8.8 Hz), 96.5 (d, 7 = 14.6 Hz), 66.4, 63.6, 61.5 (d, 7 = 7.4 Hz), 51.1, 49.0 (d, 7 = 8.7 Hz), 46.8-45.8 (m), 37.4, 34.2-33.9 (m), 28.7, 28.2, 22.6, 20.6, 14.2 ppm. ,lP NMR (81 MHz, CDCI3): δ 18.9 ppm. Elementaranalyse (%) für C67H54BF24IrNP: ber.: C 51.48, H 3.48, N 0.90. gef: C 51.55, H 3.39, N 0.84.12.6 Hz), 133.6 (d, 7 = 9.3 Hz), 132.1-122.8 (m), 119.5, 117.8, 93.7 (d, J = 8.8 Hz), 96.5 (d, 7 = 14.6 Hz), 66.4, 63.6, 61.5 (d, 7 = 7.4 Hz), 51.1, 49.0 (d, 7 = 8.7 Hz), 46.8-45.8 (m), 37.4, 34.2-33.9 (m), 28.7, 28.2, 22.6, 20.6, 14.2 ppm. , l P NMR (81 MHz, CDCI 3 ): δ 18.9 ppm. Elemental analysis (%) for C 67 H 54 BF 24 IrNP: calc .: C 51.48, H 3.48, N 0.90. found: C 51.55, H 3.39, N 0.84.
Beispiel 23Example 23
[Ir(17)(cod)]BARF[Ir (17) (cod)] BARF
Analog zu Beispiel 22 wurde vorstehend genanntes Produkt ausgehend vomAnalogously to Example 22, the product mentioned above was started from
Liganden aus Beispiel 17 in einer Ausbeute von 88 % d. Th. erhalten.Ligands from Example 17 in a yield of 88% of theory. Th. Received.
Mp: 86-92°C 13C NMR (75 MHz, CDCI3): δ 163.3-159.7 (m), 137.9-121.1 (m), 116.5-116.4 (m),Mp: 86-92 ° C 13 C NMR (75 MHz, CDCI 3 ): δ 163.3-159.7 (m), 137.9-121.1 (m), 116.5-116.4 (m),
80.0 (d, 7= 3.1 Hz), 75.7, 70.7 (d, 7= 23.7 Hz), 63.4, 55.5, 44.4 (d, 7= 5.3 Hz), 39.680.0 (d, 7 = 3.1 Hz), 75.7, 70.7 (d, 7 = 23.7 Hz), 63.4, 55.5, 44.4 (d, 7 = 5.3 Hz), 39.6
(d, 7= 27.3 Hz), 36.6, 34.5 (d, 7= 5.6 Hz), 31.5 (d, J= 8.1 Hz), 27.1, 26.3, 22.0 (d, 7(d, 7 = 27.3 Hz), 36.6, 34.5 (d, 7 = 5.6 Hz), 31.5 (d, J = 8.1 Hz), 27.1, 26.3, 22.0 (d, 7
= 3.9 Hz), 19.8, 19.5, 13.9 Hz ppm.= 3.9 Hz), 19.8, 19.5, 13.9 Hz ppm.
31P NMR (81 MHz, CDC13): δ 19.9 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 19.9 ppm.
Beispiel 24Example 24
[Ir(18)(cod)]BARF[Ir (18) (cod)] BARF
Analog zu Beispiel 21 wurde vorstehend genanntes Produkt ausgehend vomAnalogously to Example 21, the product mentioned above was started from
Liganden aus Beispiel 18 in einer Ausbeute von 75 % d. Th. erhalten. Mp: 154-160°CLigands from Example 18 in a yield of 75% of theory. Th. Received. Mp: 154-160 ° C
13C NMR (75 MHz, CDC13): δ 164.1-161.1 (m), 152.0, 139.7, 135.2, 130.3-128.6 (m), 126.7, 124.8, 123.0, 119.5, 117.8, 89.8 (d, 7 = 8.1 Hz), 87.2 (d, J = 14.5 Hz), 64.9, 61.7 (d, 7= 6.4 Hz), 59.1, 50.6, 48.4 (d, 7= 7.7 Hz), 47.9 (d, 7= 4.2 Hz), 41.7, 41.4, 40.5, 38.2, 36.4 (d, 7- 19.5 Hz), 33.4, 31.7-25.9 (m), 21.5, 20.5, 14.1 ppm: 13 C NMR (75 MHz, CDC1 3 ): δ 164.1-161.1 (m), 152.0, 139.7, 135.2, 130.3-128.6 (m), 126.7, 124.8, 123.0, 119.5, 117.8, 89.8 (d, 7 = 8.1 Hz ), 87.2 (d, J = 14.5 Hz), 64.9, 61.7 (d, 7 = 6.4 Hz), 59.1, 50.6, 48.4 (d, 7 = 7.7 Hz), 47.9 (d, 7 = 4.2 Hz), 41.7, 41.4, 40.5, 38.2, 36.4 (d, 7- 19.5 Hz), 33.4, 31.7-25.9 (m), 21.5, 20.5, 14.1 ppm:
31P NMR (81 MHz, CDC13): δ 14.3 ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 14.3 ppm.
Beispiel 25Example 25
[Ir(19)(cod)]BARF[Ir (19) (cod)] BARF
Analog zu Beispiel 21 wurde vorstehend genanntes Produkt ausgehend vom Liganden aus Beispiel 19 in einer Ausbeute von 88 % d. Th. erhalten. Mp: 165-169°C 13C NMR (75 MHz, CDC13): δ 165.2-162.8 (m), 153.4, 141.4, 137.8 (d, 7 = 53.1Analogously to Example 21, the product mentioned above was started from the ligand from Example 19 in a yield of 88% of theory. Th. Received. Mp: 165-169 ° C 13 C NMR (75 MHz, CDC1 3 ): δ 165.2-162.8 (m), 153.4, 141.4, 137.8 (d, 7 = 53.1
Hz), 136.9, 136.4 (d, 7 = 12.5 Hz), 135.3 (d, 7 = 9.4 Hz), 133.9-133.6 (m), 132.1- 130.3 (m), 128.5, 126.6, 125.2-124.6 (m), 119.6-119.5 (m), 95.6 (d, J= 8.7 Hz), 94.3 (d, 7= 15.0 Hz), 68.2, 65.3, 63.3 (d, 7= 7.5 Hz), 52.8, 50.7 (d, 7= 8.5 Hz), 48.6 (d, 7 = 3.8 Hz), 47.7 (d, 7= 26.3 Hz), 39.1 (d, 7= 3.6 Hz), 36.3-35.6 (m), 30.5, 29.9, 28.9, 28.5, 24.3, 22.4, 14.2 ppm.Hz), 136.9, 136.4 (d, 7 = 12.5 Hz), 135.3 (d, 7 = 9.4 Hz), 133.9-133.6 (m), 132.1- 130.3 (m), 128.5, 126.6, 125.2-124.6 (m), 119.6-119.5 (m), 95.6 (d, J = 8.7 Hz), 94.3 (d, 7 = 15.0 Hz), 68.2, 65.3, 63.3 (d, 7 = 7.5 Hz), 52.8, 50.7 (d, 7 = 8.5 Hz), 48.6 (d, 7 = 3.8 Hz), 47.7 (d, 7 = 26.3 Hz), 39.1 (d, 7 = 3.6 Hz), 36.3-35.6 (m), 30.5, 29.9, 28.9, 28.5, 24.3, 22.4, 14.2 ppm.
31P NMR (81 MHz, CDCI3): δ 18.9 ppm. 31 P NMR (81 MHz, CDCI 3 ): δ 18.9 ppm.
Beispiel 26Example 26
[Ir(20)(cod)]BARF[Ir (20) (cod)] BARF
Analog zu Beispiel 21 wurde vorstehend genanntes Produkt ausgehend vom Liganden aus Beispiel 20 in einer Ausbeute von 85 % d. Th. erhalten. Mp: 85-90°C 1H NMR (200 MHz, CDC13): δ 8.62-8.54 (m, 1H), 7.80-7.00 (m, 25H), 4.86-4.62 (m, 1H), 4.56-4.42 (m, 1H), 4.36-4.20 (m, 1H), 3.90-3.78 (m, 1H), 3.10-2.90 (m, 1H), 2.80-1.00 (m, 18H), 0.85 (s, 3H) ppm. 3αP NMR (81 MHz, CDC13): δ 11.7 ppm.Analogously to Example 21, the product mentioned above was started from the ligand from Example 20 in a yield of 85% of theory. Th. Received. Mp: 85-90 ° C 1H NMR (200 MHz, CDC1 3 ): δ 8.62-8.54 (m, 1H), 7.80-7.00 (m, 25H), 4.86-4.62 (m, 1H), 4.56-4.42 (m, 1H), 4.36-4.20 (m, 1H), 3.90-3.78 (m, 1H), 3.10-2.90 (m, 1H), 2.80-1.00 (m, 18H), 0.85 (s, 3H) ppm. 3α P NMR (81 MHz, CDC1 3 ): δ 11.7 ppm.
Beispiel 27Example 27
[Ir(16)(cod)]PF6 [Ir (16) (cod)] PF 6
Analog zu Beispiel 22 wurde vorstehend genanntes Produkt ausgehend vomAnalogously to Example 22, the product mentioned above was started from
Liganden aus Beispiel 16 jedoch unter Verwendung von Animomumhexafluoro- phosphat in einer Ausbeute von 80 % d. Th. erhalten. Mp: 217-220°CLigands from Example 16, however, using animomum hexafluorophosphate in a yield of 80% of theory. Th. Received. Mp: 217-220 ° C
31P NMR (81 MHz, CDC13): δ 19.5, -143.1 (quint, 7= 713 Hz) ppm. 31 P NMR (81 MHz, CDC1 3 ): δ 19.5, -143.1 (quint, 7 = 713 Hz) ppm.
Enantioselektive Hydrierung von Olefmen und IminenEnantioselective hydrogenation of olefins and imines
Beispiele 28-48Examples 28-48
Hydrierung von:Hydrogenation of:
.E-l^-Diphenylpropen (Sl) (E)-2-(4-Methoxyphenyl)-l-phenylpropen (S2), 3-Phenyl-2-butensäureethylester (S3), 3-Phenyl-2-methylallylaIkohol (S4),.E-l ^ -diphenylpropene (S1) (E) -2- (4-methoxyphenyl) -l-phenylpropene (S2), 3-phenyl-2-butenoic acid ethyl ester (S3), 3-phenyl-2-methylallyl alcohol (S4),
3-Phenyl-2-methylalIylacetat (S5), N-Acetylphenylalanin-methylester ((S6) und N-Phenyl-benzophenonimin (S7)3-phenyl-2-methylalyl acetate (S5), N-acetylphenylalanine methyl ester ((S6) and N-phenylbenzophenone imine (S7)
Der jeweilige Komplex, das Substrat (0.4 mmol) und Toluol (2 mL) wurden in einenThe respective complex, the substrate (0.4 mmol) and toluene (2 mL) were combined in one
Autoklaven gegeben. Der Autoklav wurde verschlossen, mit Wasserstoffdruck beaufschlagt und die Reaktionsmischung für einige Zeit gerührt. Das Toluol wurde abgezogen und das Rohprodukt über eine kurze Silicagel-Säule mit Pentan als Laufmittel gespült. Nach Abziehen des Lösungsmittels wurde das Produkt erhalten. Die Ergebnisse sind in Tabelle 1 dargestellt. Given autoclaves. The autoclave was sealed with hydrogen pressure applied and the reaction mixture stirred for some time. The toluene was drawn off and the crude product was rinsed on a short silica gel column using pentane as the eluent. After removing the solvent, the product was obtained. The results are shown in Table 1.
Tabelle 1: Iridium-katalysierte, enantioselektive Hydrierungen:Table 1: Iridium-catalyzed, enantioselective hydrogenations:
* Lösungsmittel CH2C12, ** Zusatz von 1 mol.-% lod Beispiele 49 und 50* Solvent CH 2 C1 2 , ** addition of 1 mol .-% iodine Examples 49 and 50
Palladium-katalysierte Allylische Aminierung von 1,3-DiphenylallylacetatPalladium-catalyzed allylic amination of 1,3-diphenylallyl acetate
Beispiel 49Example 49
Herstellung von (-)-(R^B)-N-Benzyl-(l,3-diphenyl-2-propenyl)aminPreparation of (-) - (R ^ B) -N-benzyl- (1,3-diphenyl-2-propenyl) amine
Allylpalladiumchlorid-Dimer (4.0 μmol, 1.5 mg, 1.0 mol.-%) und der Ligand aus Beispiel 20 (8.0 μmol, 3.1 mg, 2.0 mol.-%) wurden in Toluol gelöst (1 mL) und beiAllyl palladium chloride dimer (4.0 μmol, 1.5 mg, 1.0 mol .-%) and the ligand from Example 20 (8.0 μmol, 3.1 mg, 2.0 mol .-%) were dissolved in toluene (1 mL) and at
Raumtemperatur für 10 min gerührt. Eine Lösung von 3-Acetoxy-l,3-diphenyl- propen (0.4 mmol, 100 mg) in Toluol (3 mL) wurde zugesetzt und die Mischung weitere 15 min gerührt. Anschließend wurde Benzylamin (0.8 mmol, 86 mg) zugegeben und weitere 12 h bei Raumtemperatur gerührt. Es wurde mit gesättigter, wässriger NH C1-Löösung gequencht und mit Diethylether extrahiert. Die organischen Phase wurde mit H2O (10 mL) gewaschen und im Vakuum eingeengt. Der Rückstand wurde säulenchromatographisch mit 50 % Diethylether in Pentan als Laufmittel gereinigt und ergab das gewünschte Produkt (95 %, 114 mg) mit einer Enantiomerenreinheit von 87 % ee als fahlgelbes Öl.Room temperature stirred for 10 min. A solution of 3-acetoxy-1,3-diphenyl-propene (0.4 mmol, 100 mg) in toluene (3 mL) was added and the mixture was stirred for a further 15 min. Then benzylamine (0.8 mmol, 86 mg) was added and the mixture was stirred at room temperature for a further 12 h. It was quenched with saturated, aqueous NH C1 solution and extracted with diethyl ether. The organic phase was washed with H 2 O (10 mL) and concentrated in vacuo. The residue was purified by column chromatography with 50% diethyl ether in pentane as the eluent and gave the desired product (95%, 114 mg) with an enantiomeric purity of 87% ee as a pale yellow oil.
Beispiel 50Example 50
Herstellung von trans-(R)-Methyl 2 -carbomethoxy-3,5~diphenylpent-4-enolatPreparation of trans- (R) -methyl 2-carbomethoxy-3,5 ~ diphenylpent-4-enolate
Allylpalladiumchlorid-Dimer (12.5 μmol, 4.6 mg, 2.5 mol.-%), Kaliumacetat (25 μmol, 3.5 mg, 5.0 mol.-%) und der Ligand aus Beispiel 16 (25 μmol, 10 mg, 5.0 mol.-%) wurden in CH2CI2 (1 mL) gelöst und bei Raumtemperatur für 10 min gerührt. Eine Lösung von 3-Acetoxy-l,3-diphenyl-propen (0.5 mmol, 126 mg) in CH2CI2 (2 mL) und N, O-Bistrimethylsilylacetamid (1.5 mmol, 0.4 mL) wurden zu- gesetzt und die Mischung weitere 15 min gerührt. Anschließend wurde BenzylaminAllyl palladium chloride dimer (12.5 μmol, 4.6 mg, 2.5 mol%), potassium acetate (25 μmol, 3.5 mg, 5.0 mol%) and the ligand from Example 16 (25 μmol, 10 mg, 5.0 mol%) were dissolved in CH 2 CI 2 (1 mL) and stirred at room temperature for 10 min. A solution of 3-acetoxy-1,3-diphenyl-propene (0.5 mmol, 126 mg) in CH 2 CI 2 (2 mL) and N, O-bistrimethylsilylacetamide (1.5 mmol, 0.4 mL) were added and the mixture stirred for a further 15 min. Subsequently, benzylamine
(0.8 mmol, 86 mg) zugegeben und weitere 12 h bei Raumtemperatur gerührt. Es wurde mit gesättigter, wässriger NH4C1-Lösung gequencht' und mit Diethylether extrahiert. Die organischen Phase wurde mit H2O (10 mL) gewaschen und im Vakuum eingeengt. Der Rückstand wurde säulenchromatographisch mit 25 % Ethylacetat in Pentan als Laufmittel gereinigt und ergab das gewünschte Produkt (75 %, 122 mg) mit einer Enantiomerenreinheit von 96 % ee als fahlgelbes Öl.(0.8 mmol, 86 mg) was added and the mixture was stirred at room temperature for a further 12 h. It was quenched with saturated, aqueous NH 4 C1 solution and extracted with diethyl ether. The organic phase was washed with H 2 O (10 mL) and concentrated in vacuo. The residue was purified by column chromatography with 25% ethyl acetate in pentane as the eluent and gave the desired product (75%, 122 mg) with an enantiomeric purity of 96% ee as a pale yellow oil.
Beispiele 51-53Examples 51-53
Iridium-katalysierte asymmetrische HydroborierungIridium-catalyzed asymmetric hydroboration
Herstellung von (N,N-Dibenzylcarbonyloxy)-4,5-diazanorbornan-l-olPreparation of (N, N-dibenzylcarbonyloxy) -4,5-diazanorbornan-l-ol
[Ir(cod)Cl]2 (3.4 mg, 0.005 mmol), Ligand (0.011 mmol) und (N,N-Dibenzyl- carbonyloxy)-4,5-diazanorbornen (0.18 g, 0.5 mmol) wurden unter Argon zusammen mit entgastem THF (0.85 mL) bei -50°C in einen Schlenkkolben gegeben. Die[Ir (cod) Cl] 2 (3.4 mg, 0.005 mmol), ligand (0.011 mmol) and (N, N-dibenzylcarbonyloxy) -4,5-diazanorbornene (0.18 g, 0.5 mmol) were degassed under argon together with degassed THF (0.85 mL) at -50 ° C in a Schlenk flask. The
Reaktionsmischung wurde für 30 min bei Raumtemperatur gerührt und dann auf 0°C abgekühlt. Es wurde Catecholboran (0.11 mL, 1 mmol) zugegeben und für 4 weitere Stunden gerührt. EtOH (0.5 mL), 3M wässrige NaOH (0.85 mL) und 30 % H2O2 (0.5 mL) wurden zugegeben und die resultierende Mischung über Nacht gerührt. Nach Extraktion mit Ethylacetat (3x10 mL) wurden die vereinigten organischen Phasen mitThe reaction mixture was stirred at room temperature for 30 min and then cooled to 0 ° C. Catecholborane (0.11 mL, 1 mmol) was added and the mixture was stirred for a further 4 hours. EtOH (0.5 mL), 3M aqueous NaOH (0.85 mL) and 30% H 2 O 2 (0.5 mL) were added and the resulting mixture was stirred overnight. After extraction with ethyl acetate (3x10 mL), the combined organic phases were added
IM wässriger NaOH (5x10 mL) und gesättigter Kochsalzlösung gewaschen und anschcließend eingeengt. Der Rückstand wurde säulenchromatographisch mit 50 % Ethylacetat in Cyclohexan als Laufmittel gereinigt und ergab den gewünschten enantiomerenangereicherten Alkohol. Die Ergebnise für verschiedene Liganden sind in Tabelle 2 angegeben. Tabelle 2: Iridium-katalysierte Hydrierung von (N,N-Dibenzylcarbonyloxy)-4,5- diazanorbornenWashed in aqueous NaOH (5x10 mL) and saturated saline and then concentrated. The residue was purified by column chromatography with 50% ethyl acetate in cyclohexane as the eluent and gave the desired enantiomerically enriched alcohol. The results for different ligands are given in Table 2. Table 2: Iridium-catalyzed hydrogenation of (N, N-dibenzylcarbonyloxy) -4,5-diazanorbornen

Claims

Patentansprtiche Patentansprtiche
1. Verbindungen der Formel (I),1. Compounds of formula (I)
in der in the
*1, *2 jeweils unabhängig voneinander ein stereogenes Kohlenstoffatom markieren, das in R- oder S- Konfiguration vorliegt,* 1, * 2 each independently mark a stereogenic carbon atom that is in the R or S configuration,
R1 und R2 jeweils unabhängig voneinander für einen gegebenenfalls substituierten Kohlenwasserstoffrest mit insgesamt 1 bis 18 Kohlenstoffatomen stehenR 1 and R 2 each independently represent an optionally substituted hydrocarbon radical with a total of 1 to 18 carbon atoms
• Het für gegebenenfalls substituiertes Azoaryl steht und• Het stands for optionally substituted azoaryl and
• A* für einen carbodivalenten, cyclischen und gegebenenfalls substituierten Rest mit insgesamt 5 bis 18 Kohlenstoffatomen steht, der für sich als Symmetrieelement keine Spiegelebene besitzt.• A * represents a carbodivalent, cyclic and optionally substituted radical with a total of 5 to 18 carbon atoms, which as a symmetry element has no mirror plane.
2. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, dass sie stereo- isomerenangereichert sind.2. Compounds according to claim 1, characterized in that they are enriched in stereo isomers.
3. Verbindungen nach Ansprach 2, dadurch gekennzeichnet, dass der relative Stoffmengenanteil nur eines Stereoisomeren bezogen auf die Summe aller3. Compounds according spoke 2, characterized in that the relative molar fraction of only one stereoisomer based on the sum of all
Stereoisomeren mindestens 98,5 % beträgt.Stereoisomers is at least 98.5%.
4. Verbindungen nach mindestens einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass R1 und R2 jeweils unabhängig voneinander für Cι-C20- Alkyl, CrCzo-Fluoralkyl, C2-C20-Alkenyl, C4-C24-Aryl, C5-C25-Arylalkyl oder C6-C26- Arylalkenyl oder zusammen für einen cyclischen Rest mit insgesamt 4 bis 20 Kohlenstoffatomen stehen.4. Compounds according to at least one of claims 1 to 3, characterized in that R 1 and R 2 are each independently of one another for C 1 -C 20 - Alkyl, CrCzo-fluoroalkyl, C 2 -C 20 alkenyl, C 4 -C 24 aryl, C 5 -C 25 arylalkyl or C 6 -C 26 arylalkenyl or together represent a cyclic radical with a total of 4 to 20 carbon atoms ,
5. Verbindungen nach mindestens einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass es folgende sind:5. Compounds according to at least one of claims 1 to 5, characterized in that they are the following:
2-[(15,2i?,3i?,45)-3-(Diphenylphosphino)-l,7,7-trimethylbicyclo[2.2.1]hept-2- yl]-pyridin,2 - [(15.2i?, 3i?, 45) -3- (diphenylphosphino) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] pyridine,
2-[(15,2i?,35,45)-3-(Diphenylphosphino)-l,7,7-trimethylbicyclo[2.2.1]-hept- "2-yl]-6-phenyl-pyridin,2 - [(15.2i?, 35.45) -3- (diphenylphosphino) -l, 7,7-trimethylbicyclo [2.2.1] -hept- " 2-yl] -6-phenyl-pyridine,
2-[(15,2i?,35,45)-3-(Diphenylphosphino)-l,7,7-tri-methyl-bicyclo-[2.2.1]- hept-2-yl]-chinolin,2 - [(15.2i?, 35.45) -3- (diphenylphosphino) -l, 7,7-tri-methyl-bicyclo- [2.2.1] - hept-2-yl] -quinoline,
2-[(15,2i?,3i?,45)-3-(Dicyclohexylphosphino)-l,7,7-trimethylbicyclo[2.2.1]- hept-2-yl] -pyridin, 2-[(15,2i?,35,5i?)-3-(Diphenylphosphino)-6,6-dimethyl-bicyclo[3.1.1]hept-2- yl] -pyridin und2 - [(15.2i?, 3i?, 45) -3- (dicyclohexylphosphino) -l, 7,7-trimethylbicyclo [2.2.1] - hept-2-yl] pyridine, 2 - [(15.2i ?, 35.5i?) - 3- (Diphenylphosphino) -6,6-dimethyl-bicyclo [3.1.1] hept-2-yl] pyridine and
2-[(15,2i?,35,5i?)-3-(Diphenyl-phosphino)-6,6-dimethylbicyclo[3.1.1]hept-2- yl] -6-phenyl-pyridin.2 - [(15.2i?, 35.5i?) - 3- (Diphenyl-phosphino) -6,6-dimethylbicyclo [3.1.1] hept-2-yl] -6-phenyl-pyridine.
6. Verbindungen der Formel (IN),6. Compounds of the formula (IN),
in der in the
Het und A* die in Anspruch 1 genannte Bedeutung besitzen.Het and A * have the meaning given in claim 1.
8. Nerbindungen nach Anspruch 7, dadurch gekennzeichnet, dass es folgende sind: 2-[(15,25,3i?, 5)-3-(Diphenylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept- 2-yl]pyridin,8. Nerbindungen according to claim 7, characterized in that there are the following: 2 - [(15,25,3i?, 5) -3- (diphenylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] pyridine,
2-[(15,2i?,35,45)-3-(Diphenylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept- 2-yl] -6-phenylpyridin, 2-[(15,25,3i?,45)-3-(Dicyclohexylphosρhoryl)-l,7,7- trimethylbicyclo[2.2.1]hept-2-yl]pyridin,2 - [(15.2i?, 35.45) -3- (diphenylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] -6-phenylpyridine, 2 - [(15.25 , 3i?, 45) -3- (dicyclohexylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] pyridine,
2-[(15,25,3i?,45)-3-(Diphenylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept- 2-yl]chinolin,2 - [(15,25,3i?, 45) -3- (diphenylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] quinoline,
2-[(15,2i?,35,5i?)-3-(Diphenylphosphoryl)-6,6 -dimethylbicyclo[3.1. l]hept-2- yljpyridin und2 - [(15.2i?, 35.5i?) - 3- (Diphenylphosphoryl) -6.6 -dimethylbicyclo [3.1. l] hept-2-ylpyridine and
2-[(15,2i?,35,5i?)-3-(Diphenylphosphoryl)-6,6-dimethylbicyclo[3.1. l]hept-2- yl] -6-ρhenyl-pyridrn.2 - [(? 15,2i, 35,5i?) - 3- (diphenylphosphoryl) -6,6-dimethyl [3.1. l] hept-2-yl] -6-ρhenyl-pyridrn.
9. Verbindungen der Formel (VIT),9. Compounds of the formula (VIT),
H H
in derin the
2*, Het, A*, R1 und R2 die in Anspruch 1 genannte Bedeutung besitzen.2 *, Het, A *, R 1 and R 2 have the meaning given in claim 1.
10. Verbindungen nach Ansprach 9, dadurch gekennzeichnet, dass es folgende sind: 2-[(15,25,3i?,45)-3-(Dipheny]phosphoryl)-l,7,7-xrimethylbicyclo[2.2.1]hept-10. Compounds according spoke 9, characterized in that they are the following: 2 - [(15,25,3i?, 45) -3- (Dipheny] phosphoryl) -l, 7,7-xrimethylbicyclo [2.2.1] hept -
2-yl]pyridin,2-yl] pyridine,
2-[(15,2i?,35,45)-3-(Diphenylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept- 2-yl] -6-phenylρyridin, 2-[(15,25,3i?,45)-3-(Dicyclohexylphosphoryl)- 1 ,7,7- trimethylbicyclo[2.2.1]hept-2-yl]pyridin,2 - [(15.2i?, 35.45) -3- (diphenylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] -6-phenylpyridine, 2 - [(15,25,3i?, 45) -3- (dicyclohexylphosphoryl) -1,7,7-trimethylbicyclo [2.2.1] hept-2-yl] pyridine,
2-[(15,25,3i?,45)-3-(Diphenylphosphoryl)-l,7,7-trimethylbicyclo[2.2.1]hept- 2-yl]chinolin, 2-[(15,2i?,35,5i?)-3-(Diρhenylphosphoryl)-6,6-dimethylbicyclo[3.1. l]hept-2- yljpyridin und2 - [(15,25,3i?, 45) -3- (diphenylphosphoryl) -l, 7,7-trimethylbicyclo [2.2.1] hept-2-yl] quinoline, 2 - [(15,2i?, 35 , 5i?) - 3- (Diρhenylphosphoryl) -6,6-dimethyl [3.1. l] hept-2-ylpyridine and
2-[(15,2i?,35,5i?)-3-(Diphenylphosphoryl)-6,6-dimethylbicyclo[3.1.1]hept-2- yl] -6-phenyl-ρyridin.2 - [(15.2i?, 35.5i?) - 3- (Diphenylphosphoryl) -6,6-dimethylbicyclo [3.1.1] hept-2-yl] -6-phenyl-pyridine.
11. Ubergangsmetallkomplexe enthaltend Verbindungen nach einem oder mehreren der Ansprüche 1 bis 6.11. transition metal complexes containing compounds according to one or more of claims 1 to 6.
12. Ubergangsmetallkomplexe nach Anspruch 11, dadurch gekennzeichnet, dass Ubergangsmetallkomplexe Komplexe von Ruthenium, Osmium, Cobalt, Rhodium, Iridium, Nickel, Palladium, Platin und Kupfer sind.12. transition metal complexes according to claim 11, characterized in that transition metal complexes are complexes of ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium, platinum and copper.
13. Katalysatoren enthaltend Ubergangsmetallkomplexe nach mindestens einem der Ansprüche 11 bis 12.13. Catalysts containing transition metal complexes according to at least one of claims 11 to 12.
14. Verwendung von Katalysatoren nach Anspruch 13 für 1 ,4- Additionen, allylische Substitutionen, Hydroborierungen, Hydroformylierungen, Hydro- cyanierungen, Heck-Reaktionen und Hydrogenierungen.14. Use of catalysts according to claim 13 for 1, 4- additions, allylic substitutions, hydroboration, hydroformylation, hydrocyanation, Heck reactions and hydrogenation.
15. Verfahren zur Herstellung von stereoisomerenangereicherten Nerbindungen, dadurch gekennzeichnet, dass die stereoisomerenangereicherten Nerbindungen entweder durch katalytische Hydrierung von Olefmen, Enaminen, Enamiden, Iminen oder Ketonen oder durch Hydroborierung von Alkenen und gegebenenfalls anschließende Oxidation oder durch allylische Substitution erhalten werden und als Katalysatoren solche nach Ansprach 13 verwendet werden. 15. A process for the preparation of stereoisomer-enriched Nerbindungen, characterized in that the stereoisomer-enriched Nerbindungen either by catalytic hydrogenation of olefms, enamines, enamides, imines or ketones or by hydroboration of alkenes and optionally subsequent oxidation or by allylic substitution and obtained as catalysts after such Speech 13 can be used.
6. Nerfahren zur Herstellung von stereoisomerenangereicherten Wirkstoffen von Arzneimitteln und Agrochemikahen, oder Zwischenprodukten dieser beiden Klassen, dadurch gekennzeichnet, dass als Katalysatoren solche nach Anspruch 13 verwendet werden. 6. Nerfahren for the production of stereoisomerically enriched active ingredients of pharmaceuticals and agrochemicals, or intermediates of these two classes, characterized in that those according to claim 13 are used as catalysts.
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