WO2007020221A2 - Amino-phosphinoalkyl-ferrocenes et leur utilisation comme ligands dans des catalyseurs pour reactions asymetriques - Google Patents

Amino-phosphinoalkyl-ferrocenes et leur utilisation comme ligands dans des catalyseurs pour reactions asymetriques Download PDF

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WO2007020221A2
WO2007020221A2 PCT/EP2006/065197 EP2006065197W WO2007020221A2 WO 2007020221 A2 WO2007020221 A2 WO 2007020221A2 EP 2006065197 W EP2006065197 W EP 2006065197W WO 2007020221 A2 WO2007020221 A2 WO 2007020221A2
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alkyl
alkoxy
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compound
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WO2007020221A3 (fr
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Antonio Togni
Andreas Bertogg
Ulrike Nettekoven
Mauro Perseghini
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Solvias Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F17/00—Metallocenes
    • C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
    • C07C29/145—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones with hydrogen or hydrogen-containing gases
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the present invention relates to 1-(1'-sec-phosphinoalk-1'-yl)-2-aminoferrocenes, a process for preparing them; N,N'-bis[2-(1-sec-phosphinoalkyl)ferro ⁇ n-1-yl]formamidines, a process for preparing them; metal complexes of transition metals with these compounds as ligands; and the use of the metal complexes as asymmetric catalysts in enantioselective addition reactions onto prochiral organic compounds.
  • Chiral ferrocenediphosphines having a secondary phosphino group and a i-(sec-phosphino)- alk-1-yl group in the ortho positions of one cyclopentadienyl ring (Cp) of ferrocene have already been described as ligands for metal complexes for asymmetric synthesis, in particular the enantioselective hydrogenation of prochiral organic compounds, in the US patents 5,463,097, 5,466,844 and 5,583,241. They can correspond to the formula
  • s-Phos is sec-phoshino.
  • Compounds in which the s-Phos bound to the Cp ring in the above formula has been replaced by an amino group are not known and processes for preparing such compounds have not been described.
  • Such compounds can have properties which are of interest with regard to possible chiral ligands and there is interest in making them available.
  • 1-(1'-sec-phosphinoalk-1'-yl)-2-aminoferrocenes can be obtained in a few process steps starting from 1-vinyl-2-carboxylferrocene. It has also surprisingly been found that 1-(1'-sec-phosphinoalk-1'-yl)-2-aminoferrocenes are themselves chiral ligands for the formation of metal complexes which can be used as catalysts in asymmetric syntheses such as hydrogenations, with good catalytic properties in respect of activity and selectivity being observed.
  • the invention firstly provides compounds of the formula I in the form of racemates, mixtures of stereoisomers or optically pure stereoisomers,
  • R is unsubstituted or F-, Cl-, OH-, C r C 4 -alkyl- or C r C 4 -alkoxy-substituted Ci-C 8 -alkyl, C 3 -C 8 - cycloalkyl, C 3 -C 8 -cycloalkyl-Ci-C 4 -alkyl or C 7 -Ci i-aralkyl;
  • Xi is a secondary phosphino group;
  • Ri is Ci-C 4 -alkyl or phenyl; and n is 0 or from 1 to 5.
  • a Ci-C 8 -alkyl radical R can be linear or branched and an alkyl radical Ri is preferably d-C 4 - alkyl.
  • the radical can be, for example, methyl, ethyl, n- or i-propyl or n- or i-butyl or the isomers of pentyl, hexyl, heptyl and octyl.
  • substituted alkyl are fluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, hydroxymethyl, ⁇ -hydroxyethyl, methoxymethyl, ethoxymethyl and ⁇ -methoxyethyl.
  • the alkyl is preferably linear.
  • An alkyl radical Ri is preferably methyl or ethyl.
  • a cycloalkyl radical R is preferably C 5 -C 8 -cycloalkyl, preferably C 5 -C 6 -cycloalkyl. It can be, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, each of which may, for example, be substituted by F, C r C 4 -alkyl or C r C 4 -alkoxy.
  • Preferred cycloalkyl radicals are cyclopentyl and cyclohexyl.
  • a cycloalkylalkyl radical R is preferably C 5 -C 8 -cycloalkyl-Ci-C 2 -alkyl. It can be, for example, cyclopropylmethyl or cyclopropylethyl, cyclobutylmethyl or cyclobutylethyl, cyclopentyl methyl or cyclopentylethyl, cyclohexyl methyl or cyclohexylethyl, cycloheptylmethyl or cycloheptyl- ethyl or cyclooctyl methyl or cyclooctylethyl, each of which may, for example, be substituted by F, Ci-C 4 -alkyl or Ci-C 4 -alkoxy.
  • Preferred cycloalkylalkyl radicals are cyclopentylmethyl and cyclohexylmethyl.
  • An aralkyl radical R is preferably benzyl or ⁇ -phenylethyl, where the phenylethyl group may be substituted by F, Cl, Ci-C 4 -alkyl or Ci-C 4 -alkoxy.
  • R in the compounds of the formula I is methyl.
  • the secondary phosphino group Xi can contain two identical or two different hydrocarbon radicals. In the latter case, the secondary phosphino groups are P-chiral.
  • the secondary phosphino group Xi preferably contains two identical hydrocarbon radicals.
  • the hydrocarbon radicals can be unsubstituted or substituted and/or contain heteroatoms selected from the group consisting of O, S and N. They can contain from 1 to 22, preferably from 1 to 18 and particularly preferably from 1 to 14, carbon atoms.
  • a preferred secondary phosphino group is one which contains two identical or different radicals selected from the group consisting of linear or branched Ci-Ci 2 -alkyl; unsubstituted or d-C 6 -alkyl- or CrC 6 - alkoxy-substituted C 5 -Ci 2 -cycloalkyl or C 5 -Ci 2 -cycloalkyl-CH 2 -; phenyl, naphthyl, furyl and benzyl; and phenyl and benzyl substituted by halogen (for example F, Cl and Br), CrC 6 -alkyl, Ci-C 6 -haloalkyl (for example trifluoromethyl), Ci-C 6 -al
  • alkyl substituents on P which preferably contain from 1 to 6 carbon atoms, are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl and the isomers of pentyl and hexyl.
  • alkyl substituents on P are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl and the isomers of pentyl and hexyl.
  • unsubstituted or alkyl-substituted cycloalkyl substituents on P are cyclopentyl, cyclohexyl, methylcyclopentyl and ethylcyclopentyl, dimethylcyclopentyl, methylcyclohexyl and ethylcyclohexyl and dimethylcyclohexyl
  • alkyl-, alkoxy-, haloalkyl-, haloalkoxy- and halogen-substituted phenyl and benzyl substituents on P are o-, m- or p- fluorophenyl, o-, m- or p-chlorophenyl, difluorophenyl or dichlorophenyl, pentafluorophenyl, methyl phenyl, dimethyl phenyl, trimethylphenyl, ethylphenyl, methyl benzyl, methoxyphenyl, dimethoxyphenyl, trifluoromethylphenyl, bistrifluoromethylphenyl, tristrifluoromethylphenyl, trifluoromethoxyphenyl, bistrifluoromethoxyphenyl and 3,5-dimethyl-4-methoxyphenyl.
  • Preferred secondary phosphino groups are ones which contain identical radicals selected from the group consisting of CrC 6 -alkyl, unsubstituted cyclopentyl or cyclohexyl and cyclopentyl or cyclohexyl substituted by from 1 to 3 C r C 4 -alkyl or C r C 4 -alkoxy groups, benzyl and in particular phenyl which may each be unsubstituted or substituted by from 1 to 3 C r C 4 -alkyl, C r C 4 -alkoxy, F, Cl, C r C 4 -fluoroalkyl or C r C 4 -fluoroalkoxy groups.
  • the substituent F can also be present four or five times.
  • the secondary phosphino group Xi preferably corresponds, independently of one another, to the formula -PR 2 R 3 , where R 2 and R 3 are each, independently of one another, a hydrocarbon radical having from 1 to 18 carbon atoms which is unsubstituted or substituted by halogen, Ci-C 6 -alkyl, CrC 6 -haloalkyl, CrC 6 -alkoxy, CrC 6 -haloalkoxy, (Ci-C 4 -alkyl) 2 amino, (C 6 Hs) 3 Si, (C r Ci 2 -alkyl) 3 Si or -CO 2 -Ci -C 6 -alkyl and/or contains heteroatoms O.
  • R 2 and R 3 are preferably identical radicals selected from the group consisting of linear or branched Ci-C 6 -alkyl, unsubstituted cyclopentyl or cyclohexyl and cyclopentyl or cyclohexyl substituted by from one to three Ci-C 4 -alkyl or Ci-C 4 -alkoxy groups, furyl, norbomyl, adamantyl, unsubstituted benzyl and benzyl substituted by from one to three d-C 4 -alkyl or Ci-C 4 -alkoxy groups and in particular unsubstituted phenyl and phenyl substituted by from one to three C r C 4 -alkyl, C r C 4 -alkoxy, -NH 2 , -N(C r C 6 -alkyl) 2 , OH, F, Cl, C r C 4 -fluoroalkyl or Ci-C 4 -flu
  • R 2 and R 3 are particularly preferably identical radicals selected from the group consisting of Ci-C 6 -alkyl, cyclopentyl, cyclohexyl, furyl and unsubstituted phenyl and phenyl substituted by from one to three CrC 4 -alkyl, Ci-C 4 -alkoxy and/or Ci-C 4 -fluoroalkyl groups.
  • the secondary phosphino group Xi can be cyclic sec-phosphino groups, for example groups of the formulae
  • the substituents can be bound in one or both ⁇ positions relative to the P atom in order to introduce chiral carbon atoms.
  • the substituents in one or both ⁇ positions are preferably Ci-C 4 -alkyl or benzyl, for example methyl, ethyl, n- or i-propyl, benzyl or -CH 2 -O-Ci -C 4 -alkyl or -CH 2 -O-C 6 -Ci o-aryl.
  • Substituents in the ⁇ , ⁇ positions can be, for example, Ci-C 4 -alkyl, d-C 4 -alkoxy, benzyloxy or -0-CH 2 -O-, -O-CH(Ci-C 4 -alkyl)-O-, -O-C(Ci-C 4 -alkyl) 2 -O- and -O-CH(C 6 -Ci 0 -aryl)-O-.
  • Some examples are methyl, ethyl, methoxy, ethoxy, -O-CH(phenyl)-O-, -O-CH(methyl)-O- and -O-C(methyl) 2 -O-.
  • An aliphatic 5- or 6-membered ring or benzene can be fused onto two adjacent carbon atoms in the radicals of the above formulae.
  • secondary phosphino radicals are those of cyclic and chiral phospholanes having seven carbon atoms in the ring, for example those of the formulae
  • aromatic rings may be substituted by CrC 4 -alkyl, CrC 4 -alkoxy, CrC 4 -alkoxy- CrC 2 -alkyl, phenyl, benzyl, benzyloxy or Ci-C 4 -alkylidenedioxyl or C r C 4 -alkylenedioxyl (see US 2003/0073868 A1 and WO 02/048161).
  • the cyclic phosphino radicals can be C-chiral, P-chiral or C- and P-chiral.
  • the cyclic sec-phosphino group can correspond, for example, to the formulae (only one of the possible diastereomers shown),
  • radicals R' and R" are each d-C 4 -alkyl, for example methyl, ethyl, n- or i-propyl, benzyl, or -CH 2 -O-Ci -C 4 -alkyl or -CH 2 -O-C 6 -Ci 0 -aryl and R' and R" are identical or different.
  • R' and R" are bound to the same carbon atom, they can also together be C 4 -C 5 -alkylene.
  • Xi in the compounds of the formula I is preferably an acyclic secondary phosphino group selected from the group consisting of -P(Ci-C 6 -alkyl) 2 , -P(C 5 -C 8 -cycloal kyl) 2 , -P(C 7 -Ci 2 -bicycloalkyl) 2 , -P(o-furyl) 2 , -P(C 6 H 5 J 2 , -P[2-(Ci-C 6 -alkyl)C 6 H 4 ] 2j -P[3-(Ci-C 6 -alkyl)C 6 H 4 ] 2j -P[4-(Ci-C 6 -alkyl)C 6 H 4 ] 2j -P[2-(Ci-C 6 -alkoxy)C 6 H 4 ] 2j -P[3-(Ci-C 6 -alkoxy)C 6 H 4 ] 2j -P[3-
  • R' is methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, methoxymethyl, ethoxymethyl or benzyloxymethyl and R" independently has one of the meanings of R'.
  • Ri is preferably methyl
  • n in formula I is particularly preferably 0, or in other words the Cp ring then contains only hydrogen atoms.
  • the invention further provides a process for preparing the compounds of the formula I, which is characterized in that a) a compound of the formula Il
  • Ri and n are as defined above, and R 4 and R' 4 are each, independently of one another, hydrogen or unsubstituted or F-, Cl-, OH-, C r C 4 -alkyl- or C r C 4 - alkoxy-substituted Ci-C 7 -alkyl, C 3 -C 8 -cycloalkyl, C 6 -Ci 0 -aryl, C 3 -C 8 -cycloalkyl- C r C 3 -alkyl or C 7 -Ci o-aralkyl or R 4 and R' 4 together form a 3- to 8-membered carbocyclic ring which is unsubstituted or substituted by F, Cl, OH, Ci-C 4 -alkyl or Ci-C 4 -alkoxy; b) is firstly reacted at elevated temperature with diphenylphosphoryl azide of the formula (C 6 H 5 O) 2 P(O)-N 3 in the
  • R 5 is a hydrocarbon radical of an alcohol having from 1 to 20 carbon atoms
  • the compound of the formula III is reacted at elevated temperature with a secondary phosphine X r H in acetic acid solvent to form a compound of the formula IV,
  • R 5 -O-C(O)- group is a protective group for the amino group. It can also be removed by methods other than hydrolysis, for example by means of hydrogenolysis. If R 4 and R' 4 together form a carbocyclic ring, it is preferably a 5- or 6-membered ring.
  • the compounds of the formula Il can be obtained by Hoffmann degradation of the known compound 1-(dimethylamino)alk-1-yl-2-carboxylferrocene [L. Beyer et al. In J. of Organom. Chem. (1998) 561(1-2), pages 199-201] by means of methyl iodide.
  • the known vinylferrocenecarboxylic esters can be converted by means of hydrolysis into the compounds of the formula II.
  • Diphenylphosphoryl azide of the formula (C 6 Hs) 2 P(O)-N 3 is commercially available.
  • "elevated temperature” preferably means temperatures of up to 150 0 C and more preferably from 50 to 120°C.
  • the amine is preferably used in excess, for example in amounts of up to 2 equivalents and more preferably up to 1.5 equivalents, based on the compound of the formula II.
  • Diphenylphosphoryl azide is used in equimolar amounts or a slight excess, for example up to 1.2 equivalents, based on the compound of the formula II.
  • the reaction is preferably carried out in inert solvents having boiling points in the region of the selected reaction temperature.
  • solvents examples include aliphatic and aromatic hydrocarbons (methylcyclohexane, octane, benzene, toluene, xylene), halogenated hydrocarbons (methylene chloride, chloroform, dichloroethane, trichloroethane or tetrachloroethane), ethers (tetrahydrofuran, dioxane, ethylene glycol dimethyl or diethyl ether), carboxylic esters and lactones and carboxamides and lactams (dimethylformamide, N-methyl pyrrol idone).
  • the reactants and solvents can be mixed at room temperature and then heated.
  • the commencement of the reaction can be recognized by bubble formation (nitrogen gas).
  • bubble formation nitrogen gas
  • the mixture can be stirred at elevated temperature for a further time.
  • the alcohol is subsequently added at about the same temperature and the mixture is stirred further for some time.
  • the reaction mixture can be cooled, mixed with an organic solvent and water and extracted.
  • sodium azide together with pyridine or triphosgene or an azide donor such as sodium azide can be used in place of diphenylphosphoryl azide. Evaporation of the solvent and, if appropriate, purification in a customary manner gives the desired product in high yields (greater than 70% in unoptimized processes).
  • the alcohols used in process step b) can be aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, aromatic or araliphatic alcohols, for example CrCi 8 - and preferably Ci-Ci 2 -alkanols, C 3 -Ci 2 - and preferably C 3 -C 8 -cycloalkanols, C 3 -Ci 2 - and preferably C 3 -C 8 -cycloalkyl-Ci-C 3 -alkanols, phenols and C 7 -d 2 -aralkanols.
  • the aliphatic and aromatic rings may be substituted by C r Ci 8 -alkyl groups.
  • Alcohols which are not volatile at the reaction temperature are ethanol, propanol, butanol, pentanol, hexanol, cyclohexanol, methylcyclohexanol, cyclohexylmethanol, phenol, nonylphenol, benzyl alcohol and ⁇ -phenylethanol. Particular preference is given to benzyl alcohol.
  • the temperature in process step c) can be, for example, from 40 to 120 0 C, more preferably from 40 to 100°C.
  • the secondary phosphine is preferably added in excess, for example in amounts of up to 5 equivalents, based on the compound of the formula III.
  • the compound of the formula IV can, after distilling off acetic acid and excess phosphine, be isolated and purified, for example by means of recrystallization. The product is obtained in high yields and optical purity (de > 98%).
  • the hydrolysis in process step d) is advantageously carried out using aqueous alkali metal hydroxides.
  • the reaction temperature can be from 50 to 120 0 C.
  • the compound of the formula IV can be suspended in a solvent (for example alcohols such as ethanol, propanol, isopropanol, butanol) and water and a solid alkali metal hydroxide (LiOH, NaOH, KOH) can then be added.
  • a solvent for example alcohols such as ethanol, propanol, isopropanol, butanol
  • a solid alkali metal hydroxide LiOH, NaOH, KOH
  • the mixture is then stirred at elevated temperature, for example from 50 to 120 0 C, until the hydrolysis is complete.
  • the organic phase can be separated off, dried and isolated in a known manner by distilling off the solvent and drying the residue.
  • the compound of the formula I is obtained in high yields and optical purity.
  • the invention also provides the intermediates of the formulae II, III and IV.
  • the compounds of the formula I themselves are chiral ligands or they can be converted into formamidines which are likewise valuable ligands.
  • the invention further provides compounds of the formula V in the form of racemates, mixtures of stereoisomers or optically pure stereoisomers, where n, R 1 , R and Xi are as defined above, including the preferred embodiments, and R 6 is H, C r Ci 2 -alkyl or C 6 -Ci 0 -aryl.
  • the invention also provides a process for preparing the compounds of the formula V, which is characterized in that a compound of the formula I is reacted at elevated temperature with at least equivalent amounts of s-triazine or a carboxylic orthoester.
  • the s-triazine is preferably used in excess, for example in amounts of up to 8 equivalents, based on the compound of the formula IV.
  • the reaction temperature can, for example, be from 50 to 150°C, preferably from 60 to 120°C.
  • the reaction is advantageously carried out in the presence of solvents, for example the abovementioned solvents. Reactions with carboxylic orthoesters are described by E. C. Taylor et al. in J. Org. Chem. 28 (1963), pages 108-1112.
  • the compounds of the formulae I and V can be used to prepare metal complexes.
  • the metal complexes of the invention are homogeneous catalysts or catalyst precursors which can be activated under the reaction conditions which can be used for asymmetric addition reactions onto prochiral, unsaturated, organic compounds, see E. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehensive Asymmetric Catalysis I to III, Springer Verlag, Berlin, 1999, and B. Cornils et al., in Applied Homogeneous Catalysis with Organometallic Compounds, Volume 1 , Second Edition, Wiley VCH-Verlag (2002).
  • the compounds of the formulae I and V according to the invention are ligands for complexes of metals selected from among the group of TM8 metals, preferably from the group consisting of Ru, Rh and Ir, which are excellent catalysts or catalyst precursors for asymmetric syntheses, for example the asymmetric hydrogenation of prochiral, unsaturated, organic compounds. If prochiral unsaturated organic compounds are used, a very high excess of optical isomers can be induced in the synthesis of organic compounds and a high chemical conversion can be achieved in short reaction times. The achievable enantioselectivites and catalyst activities are excellent. Furthermore, such ligands can also be used in other asymmetric addition or cyclization reactions.
  • the invention further provides complexes of metals selected from among the group of transition metals of the Periodic Table (TMs) with one of the compounds of the formulae I and V as ligand.
  • TMs Periodic Table
  • Possible metals are, for example, Cu, Ag, Au, Ni, Co, Rh, Pd, Ir, Ru and Pt.
  • Preferred metals are rhodium and iridium and also ruthenium, platinum, palladium and copper.
  • Particularly preferred metals are palladium, ruthenium, rhodium and iridium.
  • the metal complexes can, depending on the oxidation number and coordination number of the metal atom, contain further ligands and/or anions. They can also be cationic metal complexes. Such analogous metal complexes and their preparation have been widely described in the literature.
  • the metal complexes can, for example, correspond to the general formulae Vl and VII
  • a 3 is one of the compounds of the formulae I and V,
  • L represents identical or different monodentate, anionic or nonionic ligands, or L represents identical or different bidentate, anionic or nonionic ligands; r is 2, 3 or 4 when L is a monodentate ligand or n is 1 or 2 when L is a bidentate ligand; z is 1, 2 or 3;
  • Me is a metal selected from the group consisting of Rh, Ir and Ru; with the metal having the oxidation state 0, 1 , 2, 3 or 4;
  • E is the anion of an oxo acid or complex acid; and the anionic ligands balance the charge of the oxidation state 1, 2, 3 or 4 of the metal.
  • Monodenate nonionic ligands can, for example, be selected from the group consisting of olefins (for example ethylene, propylene), solvating solvents (nitriles, linear or cyclic ethers, unalkylated or N-alkylated amides and lactams, amines, phosphines, alcohols, carboxylic esters, sulphonic esters), nitrogen monoxide and carbon monoxide.
  • Suitable polydentate anionic ligands are, for example, allyls (allyl, 2-methallyl), cyclopenta- dienyl or deprotonated 1,3-diketo compounds such as acetylacetonate.
  • Monodentate anionic ligands can, for example, be selected from the group consisting of halide (F, Cl, Br, I), pseudohalogenide (cyanide, cyanate, isocyanate) and anions of carboxylic acids, sulphonic acids and phosphonic acids (carbonate, formate, acetate, propionate, methylsufonate, trifluoromethylsulphonate, phenylsufonate, tosylate).
  • halide F, Cl, Br, I
  • pseudohalogenide cyanide, cyanate, isocyanate
  • carboxylic acids sulphonic acids and phosphonic acids
  • Bidentate nonionic ligands can, for example, be selected from the group consisting of linear or cyclic diolefins (for example hexadiene, cyclooctadiene, norbomadiene), dinitriles (malononitrile), unalkylated or N-alkylated carboxylic diamides, diamines, diphosphines, diols, dicarboxylic diesters and disulphonic diesters.
  • linear or cyclic diolefins for example hexadiene, cyclooctadiene, norbomadiene
  • dinitriles malononitrile
  • unalkylated or N-alkylated carboxylic diamides diamines, diphosphines, diols, dicarboxylic diesters and disulphonic diesters.
  • Bidentate anionic ligands can, for example, be selected from the group consisting of anions of dicarboxylic acids, disulphonic acids and diphosphonic acids (for example of oxalic acid, malonic acid, succinic acid, maleic acid, methylenedisul phonic acid and methylenediphosphonic acid).
  • Preferred metal complexes also include those in which E is -Cl “ , -Br “ , -I “ , CIO 4 “ , CF 3 SO 3 “ , CH 3 SO 3 “ , HSO 4 " , (CF 3 SO 2 J 2 N “ , (CF 3 SO 2 ) 3 C “ , tetraaryl borates such as B(phenyl) 4 “ , B[bis(3,5-trifluoromethyl)phenyl] 4 " , B[bis(3,5-dimethyl)phenyl] 4 " , B(C 6 F 5 ) 4 " and B(4-methylphenyl) 4 “ , BF 4 “ , PF 6 “ , SbCI 6 “ , AsF 6 “ or SbF 6 “ .
  • a 3 is one of the compounds of the formulae I and V;
  • Me is rhodium or iridium
  • Y 1 is two olefins or a diene
  • Z is Cl, Br or I
  • E 1 " is the anion of an oxo acid or complex acid.
  • Olefins Yi can be C 2 -Ci 2 -olefins, preferably C 2 -C 6 -olefins and particularly preferably C 2 -C 4 - olefins.
  • Examples are propene, 1-butene and in particular ethylene.
  • the diene can have from 5 to 12, preferably from 5 to 8, carbon atoms and can be an open-chain, cyclic or polycyclic dienes.
  • the two olefin groups of the diene are preferably connected by one or two CH 2 groups.
  • Examples are 1,4-pentadiene, cyclopentadiene, 1,5-hexadiene, 1,4-cyclohexadiene, 1 ,4- or 1,5-heptadiene, 1,4- or 1,5-cycloheptadiene, 1,4- or 1,5-octadiene, 1,4- or 1,5-cyclo- octadiene and norbomadiene.
  • Y is preferably two ethylenes or 1,5-hexadiene, 1,5-cyclo- octadiene or norbomadiene.
  • Z is preferably Cl or Br.
  • E 1 are BF 4 " , CIO 4 “ , CF 3 SO 3 “ , CH 3 SO 3 “ , HSO 4 " , B(phenyl) 4 “ , B[bis(3,5-trifluoromethyl)phenyl] 4 " , PF 6 “ , SbCI 6 “ , AsF 6 “ or SbF 6 “ .
  • the metal complexes of the invention are prepared by methods known in the literature (see also US-A-5,371 ,256, US-A-5,446,844, US-A-5,583,241 and E. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehensive Asymmetric Catalysis I to III, Springer Verlag, Berlin, 1999, and references cited therein).
  • Ruthenium complexes can, for example, correspond to the formula X,
  • a 3 is a compound of the formula I or V; L represents identical or different ligands; E " is the anion of an oxo acid, mineral acid or complex acid; S is a solvent capable of coordination as ligand; and a is from 1 to 3, b is from O to 4, c is from O to 6, d is from 1 to 3, e is from O to 4, f is from 1 to 3, g is from 1 to 4, h is from O to 6 and k is from 1 to 4, with the total charge on the complex being zero.
  • the preferences indicated above for Z, A 3 , L and E " apply to the compounds of the formula X.
  • the ligands L can additionally be arenes or heteroarenes (for example benzene, naphthalene, methyl benzene, xylene, cumene, 1 ,3,5-mesitylene, pyridine, biphenyl, pyrrole, benzimidazole or cyclopentadienyl) and metal salts having a Lewis acid function (for example ZnCI 2 , AICI 3 , TiCI 4 and SnCI 4 ).
  • the solvent ligands can be, for example, alcohols, amines, acid amides, lactams and sulphones.
  • the metal complexes of the invention are homogeneous catalysts or catalyst precursors which can be activated under the reaction conditions, which can be used for asymmetric addition reactions onto prochiral, unsaturated, organic compounds.
  • the metal complexes can, for example, be used for asymmetric hydrogenation (addition of hydrogen) of prochiral compounds having carbon-carbon or carbon-heteroatom double bonds.
  • asymmetric hydrogenation addition of hydrogen
  • metal complexes of ruthenium, rhodium and iridium are preferably used for the hydrogenation.
  • the invention further provides for the use of the metal complexes of the invention as homogeneous catalysts for preparing chiral organic compounds, preferably for the asymmetric addition of hydrogen onto a carbon-carbon or carbon-heteroatom double bond in prochiral organic compounds.
  • the invention also provides a process for preparing chiral organic compounds by asymmetric addition of hydrogen onto a carbon-carbon or carbon-heteroatom double bond in prochiral organic compounds in the presence of a catalyst, which is characterized in that the addition reaction is carried out in the presence of catalytic amounts of at least one metal complex according to the invention.
  • the prochiral unsaturated compounds can be alkenes, cycloalkenes, heterocycloalkenes or open-chain or cyclic ketones, ⁇ , ⁇ -diketones, ⁇ - or ⁇ -ketocarboxylic acids or their ⁇ , ⁇ -keto acetals or ketals, esters and amides, ketimines and kethydrazones.
  • unsaturated organic compounds are acetophenone, 4-methoxyaceto- phenone, 4-trifluoromethylacetophenone, 4-nitroacetophenone, 2-chloroacetophenone, corresponding unsubstituted or N-substituted acetophenonebenzylimines, unsubstituted or substituted benzocyclohexanone or benzocyclopentanone and corresponding imines, imines from the group consisting of unsubstituted or substituted tetrahydroquinoline, tetrahydro- pyridine and dihydropyrrole, and unsaturated carboxylic acids, esters, amides and salts, for example ⁇ - and, if appropriate, ⁇ -substituted acrylic acids or crotonic acids.
  • Preferred carboxylic acids are those of the formula
  • R 101 is d-C 6 -alkyl, unsubstituted C 3 -C 8 - cycloalkyl or C 3 -C 8 -cycloalkyl substituted by from 1 to 4 CrC 6 -alkyl, C r C 6 -alkoxy or C r C 6 - alkoxy-CrC 4 -alkoxy groups, or unsubstituted C 6 -Ci 0 -aryl, preferably phenyl, or C 6 -Ci 0 -aryl, preferably phenyl, substituted by from 1 to 4 CrC 6 -alkyl, C r C 6 -alkoxy or Ci-C 6 -alkoxy-CrC 4 - alkoxy groups, and R 102 is linear or branched CrC 6 -alkyl (for example isopropyl) or cyclo- pentyl, cyclohexyl, pheny
  • the process of the invention can be carried out at low or elevated temperatures, for example temperatures of from -20 to 150 0 C, preferably from -10 to 100 0 C and particularly preferably from 10 to 8O 0 C.
  • the optical yields are generally better at relatively low temperature than at higher temperatures.
  • the process of the invention can be carried out at atmospheric pressure or superatmos- pheric pressure.
  • the pressure can be, for example, from 10 5 to 2x10 7 Pa (pascal).
  • Hydrogenations can be carried out at atmospheric pressure or under superatmospheric pressure.
  • Catalysts are preferably used in amounts of from 0.0001 to 10 mol%, particularly preferably from 0.001 to 10 mol% and in particular from 0.01 to 5 mol%, based on the compound to be hydrogenated.
  • Suitable solvents are, for example, aliphatic, cycloaliphatic and aromatic hydrocarbons (pentane, hexane, petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, xylene), aliphatic halogenated hydrocarbons (methylene chloride, chloroform, dichloroethane and tetrachloroethane), nitriles (acetonitrile, propionitrile, benzonitrile), ethers (diethyl ether, dibutyl ether, t-butyl methyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, diox
  • the reaction can be carried out in the presence of cocatalysts, for example quaternary ammonium halides (tetrabutylammonium iodide) (see, for example, US-A-5,371 ,256, US-A-5,446,844 and US-A-5,583,241 and EP-A-O 691 949).
  • cocatalysts for example quaternary ammonium halides (tetrabutylammonium iodide)
  • fluorinated alcohols such as 1,1,1-trifluoroethanol can likewise aid the catalytic reaction.
  • a base such as an alkali metal hydroxide or alkoxide or carbonate can be advantageous.
  • the metal complexes used as catalysts can be added as separately prepared, isolated compounds or can also be formed in situ prior to the reaction and then be mixed with the substrate to be hydrogenated. It can be advantageous to add additional ligands in the reaction using isolated metal complexes or to use an excess of the ligands in the in-situ preparation. The excess can be, for example, from 1 to 6 mol, preferably from 1 to 2 mol, based on the metal compound used for the preparation.
  • the process of the invention is generally carried out by initially charging the catalyst and then adding the substrate, if desired reaction auxiliaries and the compound to be added on and subsequently starting the reaction. Gaseous compounds to be added on, for example hydrogen or ammonia, are preferably introduced under pressure. The process can be carried out continuously or batchwise in various types of reactor.
  • the chiral organic compounds which can be prepared according to the invention are active substances or intermediates for the preparation of such substances, in particular in the field of production of flavours and fragrances, pharmaceuticals and agrochemicals.
  • Bn is benzyl
  • Ph is phenyl
  • Ac is acetyl
  • the red oil obtained after filtration and evaporation of the solvent is admixed with ethanol (450 ml), water (450 ml) and sodium hydroxide (10.28 g, 256 mmol, 3 equivalents) and the mixture is stirred at 60°C for 13 hours.
  • the two-phase reaction solution is then admixed at room temperature with fert-butyl methyl ether (TBME) and acidified.
  • TBME fert-butyl methyl ether
  • the organic phase is dried over MgSO 4 , filtered and evaporated, whereupon the desired product is isolated as a yellow, amorphous solid in a yield of 15.99 g (73%).
  • a suspension of 2.39 g (4.36 mmol) of compound (4) in 30 ml of i-PrOH and 30 ml of water is degassed with the aid of an ultrasonic bath and then admixed with 16.5 g of potassium hydroxide. The mixture is stirred at 90 0 C for 17 hours and then cooled. A clear, red organic phase and a colourless aqueous phase are obtained. The organic phase is separated off and dried over MgSO 4 , then filtered and evaporated. The compound A1 is obtained in the form of a red solid in a yield of 1.66 g (92%).
  • Example C1 Hydrogenation of acetophenone using compound (B1) as ligand
  • the vessel is transferred to an autoclave and placed under an H 2 pressure of 80 bar. After stirring at room temperature for 16 hours, the autoclave is vented. A sample of the reaction mixture is taken, diluted with acetone for GC analysis, filtered and analysed by gas chromatography. This gives 55% of (S)-i-phenylethanol having an enantiomeric excess (ee) of 44%.
  • Example C2 Hydrogenation of acetophenone using compound (A1) as ligand A suspension of 19.18 mg (20.0 ⁇ mol) of dichlorotetrakis(diphenylphosphine)ruthenium(ll) and 8.52 mg (20.6 ⁇ mol) of compound (A1) in 0.5 ml of toluene is stirred at 90°C for 2 hours.

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Abstract

L'invention concerne des composés de formules (I) et (V) sous la forme de racémates, de mélanges de stéréoisomères ou de stéréoisomères optiquement purs. Dans ces formules, R est C1-C8-alkyle, C3-C8-cycloalkyl-C1-C4-alkyle ou C7-C11-aralkyle non substitué ou F-, Cl-, OH-, C1-C4-alkyl- ou C1-C4-alcoxy-substitué, X1 est un groupe phosphino secondaire, R1 est C1-C4-alkyle or phényle, et n vaut 0 ou entre 1 et 5. Ces composés sont des ligands pour la formation de complexes métalliques catalytiquement actifs utilisés comme catalyseurs homogènes asymétriques.
PCT/EP2006/065197 2005-08-12 2006-08-10 Amino-phosphinoalkyl-ferrocenes et leur utilisation comme ligands dans des catalyseurs pour reactions asymetriques WO2007020221A2 (fr)

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WO2007141662A2 (fr) * 2006-06-07 2007-12-13 Toyota Jidosha Kabushiki Kaisha Complexe amidine-acide carboxylique, composé contenant plusieurs complexes et leur méthode de production
US7982064B2 (en) 2008-11-24 2011-07-19 Brock University Method for preparing ortho-substituted aminoferrocenes
CN105859800A (zh) * 2016-04-13 2016-08-17 河南省科学院化学研究所有限公司 一种手性二茂铁类p,p配体的合成方法
CN109251227A (zh) * 2018-09-20 2019-01-22 北京师范大学 一类包含二茂铁骨架和刚性螺环结构的手性化合物及合成与应用

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Publication number Priority date Publication date Assignee Title
WO2007141662A2 (fr) * 2006-06-07 2007-12-13 Toyota Jidosha Kabushiki Kaisha Complexe amidine-acide carboxylique, composé contenant plusieurs complexes et leur méthode de production
WO2007141662A3 (fr) * 2006-06-07 2008-10-23 Toyota Motor Co Ltd Complexe amidine-acide carboxylique, composé contenant plusieurs complexes et leur méthode de production
US7982064B2 (en) 2008-11-24 2011-07-19 Brock University Method for preparing ortho-substituted aminoferrocenes
CN105859800A (zh) * 2016-04-13 2016-08-17 河南省科学院化学研究所有限公司 一种手性二茂铁类p,p配体的合成方法
CN105859800B (zh) * 2016-04-13 2018-05-29 河南省科学院化学研究所有限公司 一种手性二茂铁类p,p配体的合成方法
CN109251227A (zh) * 2018-09-20 2019-01-22 北京师范大学 一类包含二茂铁骨架和刚性螺环结构的手性化合物及合成与应用

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