WO2003061824A1 - Procede de preparation d'alcools chiraux non racemiques - Google Patents

Procede de preparation d'alcools chiraux non racemiques Download PDF

Info

Publication number
WO2003061824A1
WO2003061824A1 PCT/NL2002/000825 NL0200825W WO03061824A1 WO 2003061824 A1 WO2003061824 A1 WO 2003061824A1 NL 0200825 W NL0200825 W NL 0200825W WO 03061824 A1 WO03061824 A1 WO 03061824A1
Authority
WO
WIPO (PCT)
Prior art keywords
catalyst system
nonracemic
bis
amino
ligand
Prior art date
Application number
PCT/NL2002/000825
Other languages
English (en)
Inventor
Charles Edward Tucker
Qiongzhong Jiang
Original Assignee
Dsm Ip Assets B.V.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US10/057,826 external-priority patent/US6743921B2/en
Application filed by Dsm Ip Assets B.V. filed Critical Dsm Ip Assets B.V.
Priority to EP02786244A priority Critical patent/EP1465726A1/fr
Publication of WO2003061824A1 publication Critical patent/WO2003061824A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/0046—Ruthenium compounds
    • C07F15/0053—Ruthenium compounds without a metal-carbon linkage
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0237—Amines
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
    • B01J31/0247—Imides, amides or imidates (R-C=NR(OR))
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
    • B01J31/0251—Guanidides (R2N-C(=NR)-NR2)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0255—Phosphorus containing compounds
    • B01J31/0264—Phosphorus acid amides
    • B01J31/0265—Phosphazenes, oligomers thereof or the corresponding phosphazenium salts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/226—Sulfur, e.g. thiocarbamates
    • 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
    • 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
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
    • C07D307/42—Singly bound oxygen atoms
    • C07D307/44—Furfuryl alcohol
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/56—Radicals substituted by oxygen 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
    • C07F9/3813—N-Phosphonomethylglycine; Salts or complexes thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/821—Ruthenium
    • 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

  • This invention relates generally to preparing nonracemic chiral alcohols.
  • Nonracemic chiral alcohols are useful as pharmaceuticals and other bioactive products and as intermediates for the preparation of such products.
  • Ketones can be converted to racemic chiral alcohols by hydrogenation using certain catalyst systems of ruthenium, a phosphine ligand, a 1 ,2-diamine, and an alkaline base.
  • Aromatic and heteroaromatic ketones can be hydrogenated to nonracemic chiral alcohols by using certain catalyst systems of ruthenium, an appropriate enantiomeric diphosphine ligand, an enantiomeric 1 ,2-diamine, and an alkaline base.
  • ketones can be hydrogenated to nonracemic chiral alcohols using related catalyst systems formed with a racemic chiral 1 ,2-diamine.
  • the active diastereomeric ruthenium catalyst is formed with the enantiomeric atropisomeric diphosphine ligand and the "matched" enantiomer of the racemic chiral 1 ,2-diamine.
  • the present invention provides a catalyst system as well as a process for the preparation of a nonracemic chiral alcohol by hydrogenation of a ketone using the catalyst system.
  • the catalyst system comprises ruthenium, a nonracemic chiral diphosphine ligand, an amino-thioether ligand, and a base.
  • a chiral diamine ligand is not required to obtain highly enantioselective hydrogenation of a ketone to a nonracemic chiral alcohol when using a catalyst system comprising ruthenium, a nonracemic chiral diphosphine ligand, an amine ligand and a base.
  • the present invention provides methods for the highly enantioselective hydrogenation of a ketone to a nonracemic chiral alcohol using an amino-thioether ligand, with a catalyst system also comprising ruthenium, a nonracemic chiral diphosphine ligand, and a base.
  • the base is selected from alkylamidines, alkylguanidines, aminophosphazenes, and proazaphosphatranes.
  • the term "treating”, “contacting” or “reacting” refers to adding or mixing two or more reagents under appropriate conditions to produce the indicated and/or the desired product. It should be appreciated that the reaction which produces the indicated and/or the desired product may not necessarily result directly from the combination of two reagents which were initially added, i.e., there may be one or more intermediates which are produced in the mixture which ultimately leads to the formation of the indicated and/or the desired product. "Side-reaction” is a reaction that does not ultimately lead to a production of a desired product.
  • Alkyl means a linear saturated monovalent hydrocarbon radical or a branched saturated monovalent hydrocarbon radical or a cyclic saturated monovalent hydrocarbon radical, having the number of carbon atoms indicated in the prefix.
  • (C C 6 )alkyl is meant to include methyl, ethyl, ⁇ -propyl, 2-propyl, f ⁇ rf-butyi, pentyl, cyclopentyl, cyclohexyl and the like.
  • a divalent alkyl radical refers to a linear saturated divalent hydrocarbon radical or a branched saturated divalent hydrocarbon radical having the number of carbon atoms indicated in the prefix.
  • a divalent (C C 6 )alkyl is meant to include methylene, ethylene, propylene, 2-methylpropylene, pentylene, and the like.
  • alkenyl means a linear monovalent hydrocarbon radical or a branched monovalent hydrocarbon radical having the number of carbon atoms indicated in the prefix and containing at least one double bond.
  • (C 2 -C 6 )alkenyl is meant to include, ethenyl, propenyl, and the like.
  • Alkynyl means a linear monovalent hydrocarbon radical or a branched monovalent hydrocarbon radical containing at least one triple bond and having the number of carbon atoms indicated in the prefix.
  • (C 2 -C 6 )alkynyl is meant to include ethynyl, propynyl, and the like.
  • Alkoxy means a radical -
  • Aryl means a monocyclic or bicyclic aromatic hydrocarbon radical of 6 to 12 ring atoms which is substituted independently with one to four substituents, preferably one, two, or three substituents selected from alkyl, alkenyl, alkynyl, halo, nitro, cyano, hydroxy, alkoxy, amino, acylamino, mono-alkylamino, di-alkylamino and heteroalkyl. More specifically the term aryl includes, but is not limited to, phenyl, biphenyl, 1-naphthyl, and 2-naphthyl, and the substituted derivatives thereof.
  • Alkyl refers to a radical wherein an aryl group is attached to an alkyl group, the combination being attached to the remainder of the molecule through the alkyl portion. Examples of aralkyl groups are benzyl, phenylethyl, and the like.
  • Heteroalkyl means an alkyl radical as defined herein with one, two or three substituents independently selected from cyano, alkoxy, amino, mono- or di- alkylamino, thioalkoxy, and the like, with the understanding that the point of attachment of the heteroalkyl radical to the remainder of the molecule is through a carbon atom of the heteroalkyl radical.
  • Heteroaryl means a monocyclic or bicyclic radical of 5 to 12 ring atoms having at least one aromatic ring containing one, two, or three ring heteroatoms selected from N, O, or S, the remaining ring atoms being C, with the understanding that the attachment point of the heteroaryl radical will be on an aromatic ring.
  • the heteroaryl ring is optionally substituted independently with one to four substituents, preferably one or two substituents, selected from alkyl, alkenyl, alkynyl, halo, nitro, cyano, hydroxy, alkoxy, amino, acylamino, mono-alkylamino, di-alkylamino and heteroalkyl.
  • heteroaryl includes, but is not limited to, pyridyl, furanyl, thienyl, thiazolyl, isothiazolyl, triazolyl, imidazolyl, isoxazolyl, pyrrolyl, pyrazolyl, pyridazinyl, pyrimidinyl, benzofuranyl, tetrahydrobenzofuranyl, isobenzofuranyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, indolyl, isoindolyl, benzoxazolyl, quinolyl, tetrahydroquinolinyl, isoquinolyl, benzimidazolyl, benzisoxazolyl or benzothienyl, and the substituted derivatives thereof.
  • Hydrocarbyl is used herein to refer to an organic radical, that can be an alkyl, alkenyl, alkynyl, aryl, aralkyl, heteroalkyl or heteroaryl radical, or a combination thereof which is optionally substituted with one or more substituents generally selected from the groups noted above.
  • the present invention provides a method for the preparation of a chiral alcohol of formula II (shown without stereochemistry) from a ketone of formula I. Suitable ketones for use in the present invention are those wherein R 1 and R 2 are different, and optionally, one or both of R 1 and R 2 have a chiral center.
  • R 1 and R 2 in formulas I and II each independently represent a hydrocarbyl group that can be an acyclic, cyclic, or heterocyclic hydrocarbyl group, or a combination thereof.
  • each of the hydrocarbyl groups R 1 and R 2 can be saturated or unsaturated, including components defined above as alkyl, heteroalkyl, aryl, heteroaryl, aralkyl, alkenyl, and alkynyl groups, as well as combinations thereof.
  • each of R 1 and R 2 can be optionally substituted with one or more substituents that do not interfere with the reaction chemistry of the invention.
  • R 1 and R 2 are linked together in a cyclic structure.
  • R 1 is an optionally substituted alkyl group and R 2 is an optionally substituted aryl or heteroaryl group.
  • R 1 and R 2 can also be, independently, chiral or achiral. As used herein, however, the adjective "chiral" in the term “chiral alcohol”, specifically refers to the chirality at the carbon atom bearing each of R 1 and R 2 , which chirality is produced by the hydrogenation of the keto group at that center. The term is not meant to refer to the chirality that may be present in either R 1 or R 2 .
  • the ruthenium, nonracemic chiral diphosphine ligand, and amino- thioether ligand components of the catalyst system can be provided to the reaction mixture individually to form the reactive catalyst complex in situ or they can be provided as preformed complexes. Preformed complexes of ruthenium with the diphosphine ligand, or the amino-thioether ligand, or both can be used.
  • Examples of preformed complexes of the ruthenium with the diphosphine ligand include complexes represented by the formula RuX 2 LY n , wherein X represents a halogen atom or pseudo-halide group, preferably chloride or bromide, L represents the diphosphine ligand, Y represents a weakly coordinating neutral ligand, and n is an integer from 1 to 5.
  • Examples of Y include trialkylamines, for examples triethylamine and tetramethylethylenediamine, and tertiary amides, for example dimethylformamide.
  • Such complexes can be prepared by the reaction of the diphosphine ligand with a complex of the formula [RuX 2 (arene)] 2 , wherein examples of the arene include benzene, p-cymene, 1 ,3,5-trimethylbenzene, and hexamethylbenzene, in a solvent comprising Y.
  • Examples of preformed complexes of the ruthenium with both the diphosphine ligand and amino-thioether ligand include complexes represented by the formula RuX 2 LA, wherein A represents the amino-thioether ligand.
  • Such complexes can be prepared by the reaction of the amino-thioether with a complex of the formula RuX 2 LY n as described above.
  • the ruthenium component of the catalyst system can be provided by any ruthenium salt or complex capable of forming the active catalyst system in combination with the diphosphine ligand, the amino-thioether ligand, and the base. This can be determined by routine functional testing for ketone hydrogenation activity and enantioselectivity in the manner shown in the Examples.
  • a preferred source of the ruthenium component is a complex of the formula [RuX 2 (arene)] 2 as defined above.
  • Suitable nonracemic chiral diphosphine ligands for the present invention are bis-tertiary phosphines of the general formula R 3 R 4 PR a PR 5 R e , wherein R 3 , R 4 , R s , and R ⁇ are hydrocarbyl radicals, which may be the same or different, and R a is a hydrocarbyl diradical, any of which may be optionally linked in one or more cyclic structures.
  • Suitable hydrocarbyl groups R 3 S R , R 5 , R 6 , and diradicals thereof for R a include acyclic, cyclic, or heterocyclic hydrocarbyl groups, or combinations thereof.
  • each of the hydrocarbyl groups R 3 , R 4 S R 5 , R 6 and R a can be saturated or unsaturated, including components defined above as alkyl, heteroalkyl, aryl, heteroaryl, aralkyl, alkenyl, and alkynyl groups, as well as combinations thereof. Still further, each of R 3 , R 4 R 5 , R 6 and R a can can be optionally substituted with one or more substituents that do not undesirably affect the reaction chemistry of the invention.
  • the chirality of the diphosphine ligand may reside in one or more of the hydrocarbyl groups R 3 R 4 ⁇ R 5 , R 6 , in the bridging hydrocarbyl radical R a , at phosphorus when two hydrocarbyl radicals on phosphorus are different (R 3 ⁇ R 4 , or R 5 ⁇ R 6 , or both), or combinations thereof.
  • Chirality in the bridging hydrocarbyl diradical R a may be due to the presence of one or more stereogenic carbon atoms or due to atropoisome sm.
  • nonracemic chiral diphosphines are the enantiomers of 2,2'-bis(diphenyl-phosphino)-1 ,1'-binaphthyl (BINAP), BINAP derivatives having one or more alkyl groups or aryl groups connected to one or both naphthyl rings, BINAP derivatives having 1-5 alkyl substituents on the phenyl rings bonded to phosphorus, for example 2,2'-bis-(di-p-tolylphosphino)-1,1'-binaphthyl (TolBINAP), 5,6,7,8,5',6',7 * ,8'-octahydroBINAP (H 8 BINAP), 2,2'-bis-
  • each cycle of the bis(cyclic) structure comprises three to eight carbon atoms, and wherein the 1 , 1', 2, and 2' carbon atoms in the bis(cyclic) structure are saturated.
  • ligands are described in detail in U.S. Patent No. 6,037,500, incorporated herein by reference.
  • Preferred aryl groups in formula V are phenyl (the BICP ligand) and mono-, di-, and trialkyl-phenyl, particularly wherein alkyl is methyl, for example 2,2'-bis[di(3,5-dimethylphenyl)phosphino]-1 , 1 '-dicyclopentane (3,5-Me 8 BICP).
  • Suitable amino-thioether ligands for the present invention are of the general formula H 2 NR C SR 7 , wherein R 7 is a hydrocarbyl radical and R° is a hydrocarbyl diradical and which may be optionally linked in a cyclic structure.
  • Suitable hydrocarbyl groups R 7 and diradicals thereof for R c include acyclic, cyclic, and heterocyclic hydrocarbyl groups, include saturated and unsaturated hydrocarbyl groups, include alkyl, heteroalkyl, aryl, heteroaryl, aralkyl, alkenyl, and alkynyl groups, and can be optionally substituted with one or more substituents that do not undesirably the reaction chemistry of the invention.
  • the amino-thioether ligand may be achiral, racemic chiral, or nonracemic chiral, preferably achiral.
  • Preferred amino-thioether ligands are selected from 2- (alkylthio)ethylamines, 2-(alkylthio)anilines, and equivalents thereto that are recognized by those skilled in the art. Most preferred are 2-(alkylthio)anilines.
  • the alkyl group therein is selected from d to C alkyl groups. Most preferred are methyl and ethyl.
  • Illustrative examples include 2-(methylthio)aniline and 2-(ethylthio)aniline.
  • Suitable bases include basic inorganic and organic salts, preferably selected from basic salts comprising a cation selected from an alkali metal cation, an alkaline earth cation, and quaternary ammonium cation and a basic anion selected from hydroxide and alkoxide anions. Examples include lithium, sodium, potassium, and quaternary ammonium salts of hydroxide, methoxide, ethoxide, isopropoxide, and t-butoxide.
  • the base is selected from alkylguanidines, aminophosphazenes, proazaphosphatranes, and alkylamidines.
  • the base is preferably selected from alkylguanidines, aminophosphazenes, and proazaphosphatranes. In this embodiment, the base is most preferably selected from alkylguanidines.
  • Suitable alkylguanidines have the general formula VI, wherein R 8 , R 9 ,
  • R 10 , R 11 , and R 12 are independently selected from hydrogen and alkyl groups, with the proviso that at least one of R 8 , R 9 , R 10 , R 11 , and R 12 is an alkyl group.
  • the alkylguanidine comprises two alkyl groups, more preferably three alkyl groups, even more preferably four alkyl groups, and most preferably five alkyl groups.
  • Any of the alkyl groups R 8 , R 9 , R 10 , R 11 , and R 12 may be optionally linked in one or more cyclic structures.
  • An illustrative example of a suitable tetraalkylguanidine base is 1 ,5,7-triazabicyclo[4.4.0]dec-5-ene and tetramethylguanidine.
  • Suitable pentalkylguanidines are 7- methyl-1 ,5,7-triazabicyclo[4.4.0]dec-5-ene and tetramethyl-2-t-butylguanidine.
  • Suitable aminophosphazenes have the general formula VII, wherein R 13 is selected from hydrogen and alkyl groups, R 14 is an alkyl group and the two R 14 groups on each -NR 14 2 group may optionally be linked in a cyclic structure, and x is an integer from zero to three.
  • R 15 , R 16 , and R 17 are selected from C-, to C 8 alkyl groups, most preferably methyl.
  • An illustrative preferred proazaphosphatrane is 2,8,9-trimethyl-
  • Suitable alkylamidines have the general formula IX wherein R 18 , R 9 , and R 20 are independently selected from alkyl groups and R 21 is selected from hydrogen and alkyl groups. Preferably, R 21 is selected from alkyl groups.
  • any of the alkyl groups R 18 , R 19 , R 20 , and R 21 may be optionally linked in one or more cyclic structures.
  • An illustrative example of a suitable alkylamidine base is 1 ,5-diazabicyclo[4.3.0]non-5-ene.
  • the components of the catalyst system are each present in catalytic amounts, meaning less than stoichiometric relative to the ketone reactants.
  • the minimum amount of the catalyst system relative to the ketone reactant may depend on the activity of the specific catalyst system composition, the specific ketone to be reacted, the hydrogen pressure, the gas-liquid mixing characteristics of the reaction vessel, the reaction temperature, the concentrations of the reactants and catalyst system components in the solution, and the maximum time allowed for completion of the reaction, and can be readily determined by routine experimentation.
  • the mole ratio of the ruthenium component of the catalyst system to the ketone reactant is in the range from about 1/100 to about 1/100,000, preferably in the range from about 1/500 to about 1/10,000.
  • the mole ratio of the nonracemic diphosphine ligand to the ruthenium in the catalyst system is typically in the range from about 0.5 to about 2.0, preferably from about 0.8 to about 1.2, and most preferably is about 1.
  • the mole ratio of the amino- thioether ligand to the ruthenium in the catalyst system is typically in the range from about 1 to about 50, and preferably from about 5 to about 20.
  • the mole ratio of the base to the ruthenium in the catalyst system is typically in the range from about 1 to about 100, and preferably from about 5 to about 50.
  • the hydrogenation reaction may be conducted without solvent when the ketone itself is a liquid at the reaction temperature and capable of dissolving the catalyst system. More typically, the hydrogenation reaction is conducted in a solvent system that is capable of dissolving the catalyst system and is reaction-inert.
  • solvent system is used to indicate that a single solvent or a mixture of two or more solvents can be used.
  • reaction-inert it used to mean that the solvent system does not react unfavorably with the reactants, products, or the catalyst system. It does not mean that the solvent does not participate productively in the desired reaction.
  • the base is selected from alkylguanidines, aminophosphazenes, or proazaphosphatranes and the solvent is selected from alcohol solvents
  • the alcohol solvent levels the base. That is, these bases deprotonate the alcohol to form an alkoxide base in the reaction solution.
  • the solvent system need not bring about complete solution of the ketone reactant or the chiral alcohol product.
  • the ketone reactant may be incompletely dissolved at the beginning of the reaction or the chiral alcohol product may be incompletely dissolved at the end of the reaction, or both.
  • Representative solvents are aromatic hydrocarbons such as benzene, toluene, xylene; aliphatic hydrocarbons such as pentane, hexane, heptane; halogen- containing hydrocarbon solvents such as dichloromethane and chlorobenzene; alkyl ethers, polyethers, and cyclic ethers such as methyl-t-butyl-ether, dibutylether, diethoxymethane, 1,2-dimethoxyethane, and tetrahydrofuran; ester solvents such as ethyl acetate, organic solvents containing heteroatoms such as acetonitrile, DMF and DMSO; and alcohol solvents such as methanol, ethanol, 2-propanol, t-butanol, benzyl alcohol and the like; and mixtures thereof.
  • aromatic hydrocarbons such as benzene, toluene, xylene
  • aliphatic hydrocarbons such as
  • the solvent system comprises an alcohol solvent.
  • the alcohol solvent is 2-propanol.
  • the reaction is suitably conducted at a temperature from about -30°C to about 100°C, more typically from about 0°C to about 50°C, and most typically from about 20°C to about 40°C.
  • hydrohalogenating and “hydrogenation” refer to reacting the ketone with a source of hydrogen atoms under appropriate conditions so that two hydrogen atoms are added to the carbonyl group of the ketone to produce the hydroxyl group of the chiral alcohol.
  • the source of hydrogen atoms may be molecular hydrogen (H 2 ), a hydrogen donating organic or inorganic compound, or mixtures thereof.
  • the source of hydrogen atoms includes molecular hydrogen.
  • Hydrogen donating compounds are compounds capable of donating hydrogen atoms via the action of the catalyst system.
  • Compounds capable of donating hydrogen atoms for transfer hydrogenation reactions using ruthenium catalysts are known in the art, and include alcohols such as methanol, ethanol, n-propanol, isopropanol, butanol and benzyl alcohol, formic acid and salts thereof, unsaturated hydrocarbons and heterocyclic compounds having in part a saturated C-C bond such as tetralin, cyclohexane, and cyclohexadiene, hydroquinone, phosphorous acid, and the like.
  • the hydrogen pressure in the reaction is typically at least about 1 atm, and typically in the range from about 1 atm to about 100 atm. More typically, the hydrogen pressure is in the range from about 5 atm to about 20 atm.
  • the reaction rate and time to completion are dependent on the identities of the ketone reactant and the catalyst components, their absolute concentrations and relative ratios, the temperature, the hydrogen pressure, the gas-liquid mixing provided, and the other reaction conditions. Typically, the reaction is allowed to continue for sufficient time to complete the conversion of the ketone reactant. For typical ketone reactants, using the preferred catalyst systems described and the preferred reaction conditions described herein, the reaction is typically completed in a period of time in the range from about a few minutes to about 24 hours, more typically in the range from about 1 hour to about 10 hours.
  • the nonracemic chiral alcohol product has, by definition, a stereomeric excess greater than zero.
  • the nonracemic chiral alcohol is formed in at least about 50% stereomeric excess, more preferably at least about 60%, still more preferably at least about 70%, still again more preferably at least about 80%, and most preferably at least about 90%.
  • These stereomeric excesses refer to the chirality at the hydroxyl-bearing carbon of the alcohol group generated by the hydrogenation of the ketone group.
  • the chiral alcohol can be one of two enantiomers, and the enantiomer excess (e.e.) is the measure of stereomeric excess.
  • nonracemic diastereomer when used to refer to a nonracemic chiral alcohol product, refers to a product with an excess of one diastereomer vs. its diastereomer with the opposite chirality at the hydroxyl-bearing carbon.
  • the nonracemic diastereomer is produced in at least about 50% d.e., more preferably at least about 60% d.e., still more preferably at least about 70% d.e., still again more preferably at least about 80% d.e., and most preferably at least about 90% d.e.
  • BICP)(DMF)n] in isopropanol was prepared by dissolving the solid residue in 120 mL anhydrous, deaerated isopropanol and stored under nitrogen.
  • This Example illustrates the process of the invention wherein acetophenone is hydrogenated to nonracemic 1-phenethanol using a ruthenium catalyst system comprising a nonracemic diphosphine ligand comprising a
  • This Example illustrates the process of the invention wherein acetophenone is hydrogenated to nonracemic 1-phenethanol using a ruthenium catalyst system comprising a nonracemic diphosphine ligand comprising a
  • Example 2 shows that substantially greater activity
  • the catalyst system comprising an amino-thioether ligand.
  • Examples 1 and 2 show that the activity of the catalyst system is greater for hydrogenation using molecular hydrogen than for transfer hydrogenation using isopropanol as the sole source of hydrogen atoms, though the enantioselectivity provided by the nonracemic catalyst is comparable.
  • Examples 53-59 show the process of the invention for hydrogenation of acetophenone to nonracemic 1-phenethanol using a various based selected from alkylamidines, alkylguanidines, and aminophosphazenes.
  • the procedure was identical to Examples 1 and 2 with the exception that an equal molar amount of the base shown in Table 3 was substituted for the tetramethyl-2-t-butylguanidine (Example 1) or sodium isopropoxide (Example 2).
  • the analysis showed the conversion of the ketone was 100% and (S)- 1-phenethanol was formed in 83% e.e.
  • This Example show the process of the invention for hydrogenation of acetophenone to nonracemic 1-phenethanol using 2-butanol as the solvent.
  • the procedure was identical to Example 2 with the exceptions that 2- butanol was substituted for isopropanol in every occurrence except for the sodium isopropoxide solution and 125 microliter 0.2 M (25 micromoles) sodium isopropoxide in isopropanol was used instead of 63 microliter.
  • the analysis showed 100% conversion of the acetophenone to give S-1-phenethanol with 82% e.e.
  • Table 4 gives the diphosphine, the amino-thioether, the equivalents of sodium isopropoxide to Ru, the reaction time, the conversion of the acetophenone, the absolute configuration of the 1-phenethanol, and its e.e. [86]
  • These results demonstrate that a variety of nonracemic chiral diphosphine ligands provide the inventive catalyst systems for the hydrogenation of a ketone to a nonracemic chiral alcohol (e.e >0).
  • the results also show that different amino-thioethers give better stereoselectivities with different nonracemic chiral diphosphines and that for a given ketone reactant, a preferred combination of nonracemic chiral diphosphine and amino-thioether can be determined by routine experimentation.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention concerne un système catalytique et un procédé servant à la préparation d'un alcool chiral non racémique par hydrogénation d'une cétone, à l'aide dudit système catalytique. Le système catalytique comprend du ruthénium, un ligand diphosphine chiral non racémique, un ligand amino-thioéther et une base.
PCT/NL2002/000825 2002-01-24 2002-12-13 Procede de preparation d'alcools chiraux non racemiques WO2003061824A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02786244A EP1465726A1 (fr) 2002-01-24 2002-12-13 Procede de preparation d'alcools chiraux non racemiques

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10/057,826 US6743921B2 (en) 2002-01-24 2002-01-24 Process for the preparation of nonracemic syn-1-(4-hydroxy-phenyl)-2-(4-hydroxy-4-phenyl-piperidin-1-yl)-1-propanol compounds
US10/057,826 2002-01-24
US10/153,421 US6806378B2 (en) 2002-01-24 2002-05-21 Process for preparing nonracemic chiral alcohols
US10/153,421 2002-05-21

Publications (1)

Publication Number Publication Date
WO2003061824A1 true WO2003061824A1 (fr) 2003-07-31

Family

ID=27615967

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NL2002/000825 WO2003061824A1 (fr) 2002-01-24 2002-12-13 Procede de preparation d'alcools chiraux non racemiques

Country Status (2)

Country Link
EP (1) EP1465726A1 (fr)
WO (1) WO2003061824A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102442891A (zh) * 2010-10-12 2012-05-09 凯瑞斯德生化(苏州)有限公司 达泊西汀的中间体化合物的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0901997A1 (fr) * 1997-09-05 1999-03-17 Takasago International Corporation Procédé de préparation d'un alcool optiquement actif
US6037500A (en) * 1996-06-14 2000-03-14 The Penn State Research Foundation Asymmetric synthesis catalyzed by transition metal complexes with cyclic chiral phosphine ligands
WO2001023088A1 (fr) * 1999-09-30 2001-04-05 Dsm N.V. Catalyseur pour hydrogenation par transfert asymetrique

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6037500A (en) * 1996-06-14 2000-03-14 The Penn State Research Foundation Asymmetric synthesis catalyzed by transition metal complexes with cyclic chiral phosphine ligands
EP0901997A1 (fr) * 1997-09-05 1999-03-17 Takasago International Corporation Procédé de préparation d'un alcool optiquement actif
WO2001023088A1 (fr) * 1999-09-30 2001-04-05 Dsm N.V. Catalyseur pour hydrogenation par transfert asymetrique

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
ABDUR-RASHID K ET AL: "RUHCL(DIPHOSPHINE)(DIAMINE): CATALYST PRECURSORS FOR THE STEREOSELECTIVE HYDROGENATION OF KETONES AND IMINES", ORGANOMETALLICS, ACS, COLUMBUS, OH, US, vol. 20, no. 6, 19 March 2001 (2001-03-19), pages 1047 - 1049, XP001033320, ISSN: 0276-7333 *
AKOTSI, OKWADO M. ET AL: "Versatile precursor to ruthenium-bis(phosphine) hydrogenation catalysts", CHIRALITY (2000), 12(5/6), 514-522, XP009008808 *
CAO PING ET AL: "Ru-BICP-Catalyzed asymmetric hydrogenation of aromatic ketones", JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 64, no. 6, 19 February 1999 (1999-02-19), pages 2127 - 2129, XP002169915, ISSN: 0022-3263 *
CHANG, CHAO-WAN ET AL: "Cyclization Reactions of Ruthenium Vinylidene Complexes", ORGANOMETALLICS (1999), 18(17), 3445-3450, XP002237172 *
CHEMISTRY--A EUROPEAN JOURNAL (1997), 3(5), 713-716 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SCHENK, WOLFDIETER A. ET AL: "Enantioselective organic syntheses using chiral transition metal complexes. Part 3. Synthesis of (R)-sulforaphane using [CpRu((R,R)-CHIRAPHOS)]+ as chiral auxiliary", XP002237173, retrieved from STN Database accession no. 127:121588 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SHELDRICK, WILLIAM S. ET AL: "Bis(2-diphenylphosphinoethyl)phenylphosphineruthenium(II) complexes of amino acids and dipeptides", XP002237174, retrieved from STN Database accession no. 121:48976 *
FACHE ET AL: "Nitrogen-Containing Ligands for Asymmetric Homogenous and Heterogenous Catalysis", CHEMICAL REVIEWS, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 100, no. 6, 16 May 2000 (2000-05-16), pages 2159 - 2231, XP002201872, ISSN: 0009-2665 *
FORMAN, G. S. ET AL: "Asymmetric hydrogenation of.alpha.-ethylstyrenes catalyzed by chiral ruthenium complexes", TETRAHEDRON LETTERS (2000), 41(49), 9471-9475, XP002236691 *
HARTMANN R ET AL: "NOYORI'S HYDROGENATION CATALYSTS NEEDS A LEWIS ACID COCATALYST FOR HIGH ACTIVITY", ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, VERLAG CHEMIE. WEINHEIM, DE, vol. 40, no. 19, 1 October 2001 (2001-10-01), pages 3581 - 3585, XP001111827, ISSN: 0570-0833 *
INORGANICA CHIMICA ACTA (1994), 217(1-2), 51-9 *
NOYORI R ET AL: "ASYMMETRIC CATALYSIS BY ARCHITECTURAL AND FUNCTIONAL MOLECULAR ENGINEERING: PRACTICAL CHEMO- AND STEREOSELECTIVE HYDROGENATION OF KETONES", ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, VERLAG CHEMIE. WEINHEIM, DE, vol. 40, no. 1, January 2001 (2001-01-01), pages 41 - 73, XP000998801, ISSN: 0570-0833 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102442891A (zh) * 2010-10-12 2012-05-09 凯瑞斯德生化(苏州)有限公司 达泊西汀的中间体化合物的制备方法

Also Published As

Publication number Publication date
EP1465726A1 (fr) 2004-10-13

Similar Documents

Publication Publication Date Title
US6806378B2 (en) Process for preparing nonracemic chiral alcohols
EP2294075B1 (fr) Nouveaux complexes de ruthénium possédant des ligands amines hybrides, leur préparation et leur utilisation
Štefane et al. Advances in catalyst systems for the asymmetric hydrogenation and transfer hydrogenation of ketones
CN102858788B (zh) 钌络合物和制备光学活性醇化合物的方法
Akutagawa Enantioselective isomerization of allylamine to enamine: practical asymmetric synthesis of (–)-menthol by Rh–BINAP catalysts
WO2005097733A1 (fr) Procede pour la preparation de derives d'acides amines beta a enrichissement enantiomerique
US8716507B2 (en) Iron(II) catalysts containing diimino-diphosphine tetradentate ligands and their synthesis
US6486337B2 (en) Ruthenium-disphosphine complexes and their use as catalysts
JP2005516036A6 (ja) 非ラセミｓｙｎ−１−（４−ヒドロキシ−フェニル）−２−（４−ヒドロキシ−４−フェニル−ピペリジン−１−イル）−１−プロパノ−ル化合物の製造方法
US9255049B2 (en) Ruthenium complex and method for preparing optically active alcohol compounds using the same as a catalyst
US5892044A (en) Process for preparing optically active 1-(p-methoxybenzyl)-1,2,3,4,5,3,7,8-octahydroisoquinoline
US6207868B1 (en) Asymmetric synthesis catalyzed by transition metal complexes with chiral ligands
WO2003061826A1 (fr) Procede pour preparer des alcools chiraux non racemiques
EP1465726A1 (fr) Procede de preparation d'alcools chiraux non racemiques
WO2003061825A1 (fr) Procede de preparation d'alcools chiraux non racemiques
CA2642563C (fr) Catalyseurs a base de fer(ii) contenant des ligands de tetradentate de diimino-diphosphine, et leur synthese
EP2186812A1 (fr) Procédé de fabrication d'un dérivé de 3-quinuclidinol optiquement actif
EP1030854B1 (fr) Catalyseurs pour syntheses asymetriques contenant des ligands chiraux rigides
US20110028718A1 (en) Paracyclophane-based ligands, their preparation and use in catalysis
CA2684197A1 (fr) Catalystes de fer(ii) contenant des ligands de tetradentate diimino- diphosphine et leur synthese
CN104114539A (zh) 用于立体选择性制备吡唑甲酰胺的方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2002786244

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2002786244

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 2002786244

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP