EP1991513A2 - Organic salts and method for producing chiral organic compounds - Google Patents

Organic salts and method for producing chiral organic compounds

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Publication number
EP1991513A2
EP1991513A2 EP07721966A EP07721966A EP1991513A2 EP 1991513 A2 EP1991513 A2 EP 1991513A2 EP 07721966 A EP07721966 A EP 07721966A EP 07721966 A EP07721966 A EP 07721966A EP 1991513 A2 EP1991513 A2 EP 1991513A2
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EP
European Patent Office
Prior art keywords
chiral
reactions
scheme
anion
salts
Prior art date
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EP07721966A
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German (de)
French (fr)
Inventor
Benjamin List
Sonja Mayer
Martin Nolwenn
Wang Xingwang
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Studiengesellschaft Kohle gGmbH
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Studiengesellschaft Kohle gGmbH
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    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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    • 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
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    • 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
    • B01J31/0257—Phosphorus acids or phosphorus acid esters
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    • C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/62—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by hydrogenation of carbon-to-carbon double or triple bonds
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/69—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to carbon-to-carbon double or triple bonds
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    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
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    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
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    • C07C67/00—Preparation of carboxylic acid esters
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    • C07D301/00—Preparation of oxiranes
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    • C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
    • C07D301/14—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
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    • 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
    • B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
    • 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
    • B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
    • B01J2231/72—Epoxidation
    • 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
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
    • B01J2531/0266—Axially chiral or atropisomeric ligands, e.g. bulky biaryls such as donor-substituted binaphthalenes, e.g. "BINAP" or "BINOL"
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • 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
    • B01J31/0215—Sulfur-containing compounds
    • B01J31/0225—Sulfur-containing compounds comprising sulfonic acid groups or the corresponding salts
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    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
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    • C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered

Definitions

  • the present invention relates to a process for the preparation of chiral organic compounds.
  • the present invention accordingly provides a process for the preparation of chiral organic compounds by asymmetric catalysis, wherein ionic catalysts are used, which is characterized in that the catalyst anion of the ionic catalyst is chiral.
  • the process of the invention is mediated by salt catalysts composed of a chiral or achiral cation and a chiral anion.
  • enantiomerically enriched catalysts i. Catalysts which have an excess of a Enantionmeren, or enantiomerically pure compounds used.
  • These catalysts may e.g. be prepared by reacting a chiral or achiral base with a chiral acid.
  • the catalytic salts can also be prepared in situ from acid and base, or by other common methods known to those skilled in the art.
  • the chiral or achiral cation is preferably an ammonium compound.
  • Typical examples of catalysts according to the invention are shown in Scheme 1.
  • the catalytic salts in question catalyze reactions that proceed via cationic intermediates.
  • Such intermediates may be, for example: iminium ions, N- Acyliminium ions, acylammonium ions, phosphonium ions, sulfonium ions, oxonium ions or carbenium ions.
  • the inventive method is suitable for producing a variety of chiral compounds is not limited to any specific type of reaction.
  • Future reactions include nucleophilic additions and cycloadditions of ( ⁇ , ⁇ -unsaturated) carbonyl compounds, which proceed via cationic iminium ion intermediates, and are catalyzed by salts of primary and secondary amines (Scheme 2).
  • the catalyst used was always a salt composed of a chiral amine (as the base) and a (a) chiral acid (or the chiral amine alone).
  • the subject of this invention is the use of salts of achiral (or chiral) amines with chiral acids.
  • acyltransfer reactions which proceed via cationic, activated acyl compounds, for example acylpyridinium ions. In this way, for example, one can catalyze kinetic resolution of secondary alcohols (Scheme 3).
  • the catalyst anion according to the invention is a chiral organic or inorganic anion. Usually, it is selected from chiral organic phosphates, sulfonates, sulfates, carboxylates, imides, sulfonylimides, etc.
  • the anion is derived from unsubstituted or substituted binaphthol. Particularly good results are obtained when the anion is selected from binaphthol derivatives having the following formulas:
  • R is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aryl.
  • the cationic counterion used for the chiral anion used according to the invention may be any cation.
  • the cation is selected from alkali metal ions and ammonium ions, with ammonium ions being particularly preferred.
  • alkyl as used herein means a linear, branched or cyclic hydrocarbon radical usually having from 1 to 30, preferably from 1 to 24 carbon atoms and more preferably from 1 to 6 carbon atoms, such as methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl , t-butyl, octyl, decyl, etc., but also cycloalkyl groups such as cyclopentyl, Cyclohexyl, etc.
  • the hydrocarbon radicals have 1 to 18, in particular 1 to 12 carbon atoms.
  • aromatic ring systems having 5 to 30 carbon atoms and optionally heteroatoms such as N, O, S, P, Si, used in the ring, wherein the rings single or multiple ring systems, for. B. may be fused ring systems or single bonds or multiple bonds bonded together rings.
  • aromatic rings are phenyl, naphthyl, biphenyl, diphenyl ether, diphenylamine, benzophenone and the like.
  • Substituted aryl groups have one or more substituents.
  • heteroalkyl groups are alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylated aminoalkyl and the like.
  • heteroaryl substituents are pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl, pyrimidinyl, imidazolyl, 1, 2,4-triazolyl, tetrazolyl, and the like.
  • heteroatom-containing alicyclic groups pyrrolidino, morpholino, piperazino, piperidino, etc. may be mentioned.
  • substituents which may have the abovementioned groups, OH, F, Cl, Br, J, CN, NO 2 , NO, SO 2 , SO 3 -, amino, -COOH, -COO (C r C 6 alkyl ), Mono- and di (C r C 24 alkyl) -substituted amino, mono- and di- (C 5 -C 2 o-aryl) -substituted amino, imino, which in turn may be substituted, for example C C 1 -C 6 -alkyl, aryl, and phenyl.
  • the cyclic radicals may also have C r C 6 alkyl groups as substituents.
  • Particularly suitable anions are those which are derived from binaphtol (eg phosphates, sulfonates, sulfates, carboxylates, imides, sulfonylimides, Scheme 4).
  • binaphtol eg phosphates, sulfonates, sulfates, carboxylates, imides, sulfonylimides, Scheme 4.
  • the anions are by no means limited to these structures.
  • reaction conditions which are present for carrying out the process according to the invention depend essentially on the type of reaction chosen and can be readily adjusted by the person skilled in the art.
  • salt 1 catalyzes the highly enantioselective transfer hydrogenation of various alpha.beta-unsaturated aldehydes (2) (Scheme 6). Additional catalytic salts for the enantioselective transfer hydrogenation are shown in Schemes 7-9.
  • the aldehyde (2a-f) (1 eq) and catalyst (1a-1w) (0.2 eq for 1a, and 0.1 eq for 1b-1w, respectively) were prepared in THF (aliphatic substrates) or 1, 4-dioxane (aromatic substrates) (10 ml / mmol) and stirred for 2-5 min at room temperature (aliphatic substrates) or 50 0 C (aromatic substrates). Subsequently, Hantzsch ester (4 or 5) was added and stirred for a further 24 hours.
  • the method can also be applied to ⁇ , ⁇ -unsaturated ketones.
  • chiral phosphate salts of primary amino acid esters have proven to be powerful and highly enantioselective catalysts.
  • salt 7a catalyzes the highly enantioselective transfer hydrogenation of various alpha, beta-unsaturated ketones (9) in the presence of Hantzsch ester 8 (Scheme 12). Additional catalytic salts for the enantioselective transfer hydrogenation are shown in Schemes 13-15.
  • salt 16 is exemplary.
  • the chiral phosphoric acid (TRIP, 7.53 mg, 0.01 mmol) and DMAP (1.22 mg, 0.01 mmol) in toluene (1 ml) are stirred for one hour.
  • the racemic alcohol (0.1 mmol) and Ac 2 O (0.05 mmol, 0.5 eq) are added.
  • the product is isolated via aqueous workup.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Hydrogenated Pyridines (AREA)
  • Catalysts (AREA)
  • Epoxy Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Pyridine Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Indole Compounds (AREA)

Abstract

The invention relates to a method for producing chiral organic compounds by asymmetric catalysis, using ionic catalysts comprising a chiral catalyst anion. The claimed method is suitable for reactions which are carried out over cationic intermediate stages, such as imnium ions or acyl pyridinium ions. The invention enables the production of chiral compounds with high ee values, that until now could only be obtained by means of costly purification methods.

Description

Organische Salze sowie Verfahren zur Herstellung von chiralen organischen Organic salts and process for the preparation of chiral organic
Verbindungenlinks
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von chiralen organischen Verbindungen.The present invention relates to a process for the preparation of chiral organic compounds.
Viele chemische Transformationen verlaufen über ionische Zwischenstufen und Übergangszustände. Solche polaren Reaktionen werden durch das jeweilige Gegen-Ion beeinflusst. So kann z.B. der Verlauf von Reaktionen von Carbanionen durch Zugabe geeigneter kationischer Substanzen modifiziert werden. Dieses Prinzip ist in der so genannten Phasentransferkatalyse wohlbekannt, bei der Reaktionen von Enolaten und ähnlichen anionischen Substraten mit verschiedenen Elektrophilen asymmetrisch katalysiert werden können.Many chemical transformations proceed via ionic intermediates and transition states. Such polar reactions are influenced by the respective counter-ion. Thus, e.g. the course of reactions of carbanions can be modified by adding suitable cationic substances. This principle is well known in so-called phase transfer catalysis, in which reactions of enolates and similar anionic substrates with different electrophiles can be catalyzed asymmetrically.
D. B. Llewellyn, B. A. Arndtsen beschreiben in Tetrahedron Asymmetry 2005, 16, 1789-1799 Reaktionen mit umgekehrter Polarisierung, es konnten jedoch keine akzeptablen Enantioselektivitäten realisiert worden.D. B. Llewellyn, B.A. Arndtsen, in Tetrahedron Asymmetry 2005, 16, 1789-1799, describe reverse polarization reactions, but no acceptable enantioselectivities have been realized.
Der vorliegenden Erfindung lag demgemäß die Aufgabe zugrunde, ein Verfahren zur Herstellung von chiralen organischen Verbindungen zur Verfügung zu stellen, dass das Spektrum der durch Synthese herstellbarer chiraler Verbindungen mit hohem ee-Werten, vorzugsweise über >50%, zu erweitern und auch die Synthese von solchen Enantiomeren zu ermöglichen, die gemäß Stand der Technik nur als Enantiomerengemische erhalten werden.It is an object of the present invention to provide a process for the preparation of chiral organic compounds that extends the spectrum of the synthesis of chiral compounds with high ee values, preferably over> 50%, and also the synthesis of enable such enantiomers, which are obtained according to the prior art only as enantiomeric mixtures.
Gegenstand der vorliegenden Erfindung ist demgemäß ein Verfahren zur Herstellung von chiralen organischen Verbindungen durch asymmetrische Katalyse, wobei ionische Katalysatoren eingesetzt werden, das dadurch gekennzeichnet ist, dass das Katalysatoranion des ionischen Katalysators chiral ist.The present invention accordingly provides a process for the preparation of chiral organic compounds by asymmetric catalysis, wherein ionic catalysts are used, which is characterized in that the catalyst anion of the ionic catalyst is chiral.
Überraschenderweise wurde festgestellt, dass es mit dem erfindungsgemäßen Verfahren chirale Verbindungen in nahezu enantiomerenreiner, in den meisten Fällen mit einem ee-Surprisingly, it has been found that with the process according to the invention it is possible to obtain chiral compounds in almost enantiomerically pure, in most cases with an ee
Wert über 90%, Form herzustellen, die aus dem Stand nur durch aufwendige Reinigungsverfahren zugänglich sind. Ein Beispiel hierfür ist die hochenantioselektive Reduktion von Citral zum Parfuminhaltsstoff Citronellal.Value over 90% to produce shape that stands out only by consuming Cleaning procedures are accessible. An example of this is the highly enantioselective reduction of citral to the perfume ingredient citronellal.
Das erfindungsgemäße Verfahren wird durch Salz-Katalysatoren vermittelt, die aus einem chiralen oder achiralen Kation und einem chiralen Anion zusammengesetzt sind. In einer bevorzugten Ausführungsform werden Enantiomeren angereicherte Katalysatoren, d.h. Katalysatoren, die einen Überschuss eines Enantionmeren aufweisen, oder enantiomerenreine Verbindungen eingesetzt. Diese Katalysatoren können z.B. dadurch hergestellt werden, dass man eine chirale oder achirale Base mit einer chiralen Säure umsetzt. Alternativ, können die katalytischen Salze auch in situ aus Säure und Base hergestellt werden oder über andere gängige, dem Fachmann bekannte Methoden. Das chirale oder achirale Kation ist vorzugsweise eine Ammoniumverbindung. Typische Beispiele erfindungsgemäßer Katalysatoren sind in Schema 1 gezeigt.The process of the invention is mediated by salt catalysts composed of a chiral or achiral cation and a chiral anion. In a preferred embodiment, enantiomerically enriched catalysts, i. Catalysts which have an excess of a Enantionmeren, or enantiomerically pure compounds used. These catalysts may e.g. be prepared by reacting a chiral or achiral base with a chiral acid. Alternatively, the catalytic salts can also be prepared in situ from acid and base, or by other common methods known to those skilled in the art. The chiral or achiral cation is preferably an ammonium compound. Typical examples of catalysts according to the invention are shown in Scheme 1.
Schema 1. Auswahl möglicher Katalysatoren erfindungsgemäßer VerfahrenScheme 1. Selection of possible catalysts of the process according to the invention
Die in Frage kommenden katalytischen Salze katalysieren Reaktionen, die über kationische Zwischenstufen verlaufen. Derartige Zwischenstufen können z.B. sein: Iminiumionen, N- Acyl-iminiumionen, Acylammoniumionen, Phosphoniumionen, Sulfoniumionen, Oxoniumionen oder Carbeniumionen.The catalytic salts in question catalyze reactions that proceed via cationic intermediates. Such intermediates may be, for example: iminium ions, N- Acyliminium ions, acylammonium ions, phosphonium ions, sulfonium ions, oxonium ions or carbenium ions.
Das Erfindungsgemäße Verfahren eignet sich zu Herstellung einer Vielzahl von chiralen Verbindungen ist auf keinen konkreten Reaktionstyp beschränkt. Eine wichtige Klasse inThe inventive method is suitable for producing a variety of chiral compounds is not limited to any specific type of reaction. An important class in
Frage kommender Reaktionen sind nukleophile Additionen und Zykloadditionen von (α,ß- ungesättigten) Carbonylverbindungen, die über kationische Iminiumion Zwischenstufen verlaufen, und durch Salze primärer und sekundärer Amine katalysiert werden (Schema 2).Future reactions include nucleophilic additions and cycloadditions of (α, β-unsaturated) carbonyl compounds, which proceed via cationic iminium ion intermediates, and are catalyzed by salts of primary and secondary amines (Scheme 2).
Hierzu zählen Diels-Alder-Reaktionen, 1,3-dipolare Cycloadditionen, konjugierte Additionen, Epoxidierungen, Cyclopropanierungen, Transferhydrierungen, Mukayama-Michael-These include Diels-Alder reactions, 1,3-dipolar cycloadditions, conjugate additions, epoxidations, cyclopropanations, transfer hydrogenations, Mukayama-Michael
Additionen und Knoevenagel-Reaktionen. Das Prinzip ist jedoch nicht auf diese Reaktionen beschränkt.Additions and Knoevenagel reactions. However, the principle is not limited to these reactions.
Derartige Reaktionen konnten zwar schon asymmetrisch katalysiert werden. Als Katalysator wurde dabei aber immer ein Salz verwendet, das sich zusammensetzt aus einem chiralen Amin (als Base) und einer (a)chiralen Säure (oder das chirale Amin alleine). Gegenstand dieser Erfindung dagegen ist die Verwendung von Salzen achiraler (oder chiraler) Amine mit chiralen Säuren. Although such reactions could already be catalyzed asymmetrically. However, the catalyst used was always a salt composed of a chiral amine (as the base) and a (a) chiral acid (or the chiral amine alone). The subject of this invention, however, is the use of salts of achiral (or chiral) amines with chiral acids.
Schema 2. Auswahl möglicher Reaktionen, die nach dem erfindungsgemäßen Verfahren asymmetrisch katalysiert werden können und über Iminium Ionen verlaufen.Scheme 2. Selection of possible reactions which can be catalyzed asymmetrically by the process according to the invention and which proceed via iminium ions.
Eine andere Klasse von erfindungsgemäßen Reaktionen sind Acyltransferreaktionen, die über kationische, aktivierte Acylverbindungen, z.B. Acylpyridiniumionen, verlaufen. Auf diese Weise kann man z.B. kinetische Racematspaltungen von sekundären Alkoholen katalysieren (Schema 3). Another class of reactions according to the invention are acyltransfer reactions which proceed via cationic, activated acyl compounds, for example acylpyridinium ions. In this way, for example, one can catalyze kinetic resolution of secondary alcohols (Scheme 3).
Schema 3. Kinetische Racematspaltung via asymmetrischer Acyl-Transferreaktion als erfindungsgemäßes Verfahren.Scheme 3. Kinetic resolution by asymmetric acyl transfer reaction as a process according to the invention.
Das erfindungsgemäße Katalysatoranion ist ein chirales organisches oder anorganisches Anion. Üblicherweise wird es aus chiralen organischen Phosphaten, Sulfonaten, Sulfaten, Carboxylaten, Imiden, Sulfonylimiden etc. ausgewählt. Vorzugsweise leitet sich das Anion von unsubstituiertem oder substituiertem Binaphthol ab. Besonders gute Ergebnisse werden erhalten, wenn das Anion aus Binaphtholderivaten mit folgenden Formeln ausgewählt ist:The catalyst anion according to the invention is a chiral organic or inorganic anion. Usually, it is selected from chiral organic phosphates, sulfonates, sulfates, carboxylates, imides, sulfonylimides, etc. Preferably, the anion is derived from unsubstituted or substituted binaphthol. Particularly good results are obtained when the anion is selected from binaphthol derivatives having the following formulas:
worin wherein
R Wasserstoff, substituiertes oder unsubstituiertes Alkyl oder substituiertes oder unsubstituiertes Aryl bedeutet.R is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aryl.
Das zum erfindungsgemäß eingesetzten chiralen Anion eingesetzte kationische Gegenion kann ein beliebiges Kation sein. Vorzugsweise ist das Kation aus Alkaliionen und Ammoniumionen ausgewählt, wobei Ammoniumionen besonders bevorzugt sind.The cationic counterion used for the chiral anion used according to the invention may be any cation. Preferably, the cation is selected from alkali metal ions and ammonium ions, with ammonium ions being particularly preferred.
Der verwendete Begriff „Alkyl" bedeutet einen linearen, verzweigten oder cyclischen Kohlenwasserstoffrest, der üblicherweise 1 bis 30, vorzugsweise 1 bis 24 Kohlenstoffatome und insbesondere 1 bis 6 Kohlenstoffatome aufweist, wie Methyl, Ethyl, n-Propyl, Isopropyl, n-Butyl, Isobutyl, t-Butyl, Octyl, Decyl usw., aber auch Cycloalkylgruppen wie Cyclopentyl, Cyclohexyl usw. Vorzugsweise weisen die Kohlenwasserstoffreste 1 bis 18, insbesondere 1 bis 12 Kohlenstoffatome auf.The term "alkyl" as used herein means a linear, branched or cyclic hydrocarbon radical usually having from 1 to 30, preferably from 1 to 24 carbon atoms and more preferably from 1 to 6 carbon atoms, such as methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl , t-butyl, octyl, decyl, etc., but also cycloalkyl groups such as cyclopentyl, Cyclohexyl, etc. Preferably, the hydrocarbon radicals have 1 to 18, in particular 1 to 12 carbon atoms.
Als Arylgruppen werden im Rahmen der vorliegenden Erfindung aromatische Ringsysteme mit 5 bis 30 Kohlenstoffatomen und ggf. Heteroatomen wie N, O, S, P, Si, im Ring verwendet, wobei die Ringe einfache oder mehrfache Ringsysteme, z. B. kondensierte Ringsysteme oder über einfache Bindungen oder Mehrfachbindungen aneinander gebundene Ringe sein können. Beispiele für aromatische Ringe sind Phenyl, Naphthyl, Biphenyl, Diphenylether, Diphenylamin, Benzophenon und dergleichen. Substituierte Arylgruppen weisen einen oder mehrere Substituenten auf. Beispiele für Heteroalkylgruppen sind Alkoxyaryl, Alkylsulfanyl-substituiertes Alkyl, N-alkyliertes Aminoalkyl und dergleichen. Beispiele für Heteroarylsubstituenten sind Pyrrolyl, Pyrrolidinyl, Pyridinyl, Chinolinyl, Indolyl, Pyrimidinyl, Imidazolyl, 1 ,2,4-Triazolyl, Tetrazolyl, und dergleichen. Als Beispiele für Heteroatom-enthaltende Alicyclische Gruppen können Pyrrolidino, Morpholino, Piperazino, Piperidino usw. genannt werden.As aryl groups in the context of the present invention, aromatic ring systems having 5 to 30 carbon atoms and optionally heteroatoms such as N, O, S, P, Si, used in the ring, wherein the rings single or multiple ring systems, for. B. may be fused ring systems or single bonds or multiple bonds bonded together rings. Examples of aromatic rings are phenyl, naphthyl, biphenyl, diphenyl ether, diphenylamine, benzophenone and the like. Substituted aryl groups have one or more substituents. Examples of heteroalkyl groups are alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylated aminoalkyl and the like. Examples of heteroaryl substituents are pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl, pyrimidinyl, imidazolyl, 1, 2,4-triazolyl, tetrazolyl, and the like. As examples of heteroatom-containing alicyclic groups, pyrrolidino, morpholino, piperazino, piperidino, etc. may be mentioned.
Als Substituenten, die die voranstehend genannten Gruppen aufweisen können, kommen OH, F, Cl, Br, J, CN, NO2, NO, SO2, SO3-, Amino, -COOH, -COO(CrC6-Alkyl), Mono- und Di-(CrC24-alkyl)-substituiertes Amino, Mono- und Di-(C5-C2o-aryl)-substituiertes Amino, Imino in Betracht, die wiederum substituiert sein können, z.B. C1-C6-AIRyI, Aryl, und Phenyl. Insbesondere die cyclischen Reste können auch CrC6-Alkylgruppen als Substituenten aufweisen.As substituents which may have the abovementioned groups, OH, F, Cl, Br, J, CN, NO 2 , NO, SO 2 , SO 3 -, amino, -COOH, -COO (C r C 6 alkyl ), Mono- and di (C r C 24 alkyl) -substituted amino, mono- and di- (C 5 -C 2 o-aryl) -substituted amino, imino, which in turn may be substituted, for example C C 1 -C 6 -alkyl, aryl, and phenyl. In particular, the cyclic radicals may also have C r C 6 alkyl groups as substituents.
Als besonders geeignete Anionen haben sich solche erwiesen, die sich vom Binaphtol ableiten (z.B. Phosphate, Sulfonate, Sulfate, Carboxylate, Imide, Sulfonylimide, sie Schema 4). Die Anionen sind aber keinesfalls auf diese Strukturen beschränkt. Particularly suitable anions are those which are derived from binaphtol (eg phosphates, sulfonates, sulfates, carboxylates, imides, sulfonylimides, Scheme 4). The anions are by no means limited to these structures.
Schema 4. Auswahl möglicher erfindungsgemäßer AnionenScheme 4. Selection of possible anions according to the invention
Die Reaktionsbedingungen, die zur Durchführung des erfindungsgemäßen Verfahrens vorliegen hängen im Wesentlichen vom gewählten Reaktionstyp ab und können vom Fachmann ohne weiteres eingestellt werden.The reaction conditions which are present for carrying out the process according to the invention depend essentially on the type of reaction chosen and can be readily adjusted by the person skilled in the art.
BeispieleExamples
Primäre und sekundäre Aminsalze chiraler Phosphorsäuren . katalysieren hochenantioseiektiv die Transferhydrierung alpha, beta-ungesättigter Carbonylverbindungen mit Hilfe von Hantzsch Estern (Schema 5).Primary and secondary amine salts of chiral phosphoric acids. highly enantioselective catalyze the transfer hydrogenation of alpha, beta-unsaturated carbonyl compounds using Hantzsch esters (Scheme 5).
Schema 5. Transferhydrierung als BeispielScheme 5. Transfer hydrogenation as an example
So katalysiert das Salz 1 in Gegenwart des Hantzsch esters 4, die hochenantioselektive Transferhydrierung verschiedener alpha.beta-ungesättigter Aldehyde (2) (Schema 6). Weitere katalytische Salze für die enantioselektive Transferhydrierung sind in den Schemen 7-9 gezeigt. For example, in the presence of Hantzsch ester 4, salt 1 catalyzes the highly enantioselective transfer hydrogenation of various alpha.beta-unsaturated aldehydes (2) (Scheme 6). Additional catalytic salts for the enantioselective transfer hydrogenation are shown in Schemes 7-9.
Schema 6. Erfindungsgemäße Hochenantioselektive Transferhydrierungen. Scheme 6. Inventive high enantioselective transfer hydrogenations.
Schema 7. Hochenantioselektive Transferhydrierung. Weitere Beispiele vom Morpholinsalzen. Scheme 7. Highly enantioselective transfer hydrogenation. Further examples of morpholine salts.
Schema 8. Hochenantioselektive Transferhydrierung. Weitere Beispiele diverser 3,3'-Bis(2,4l6-trüsopropylphenyl)-1 , 1 '-binaphthyl-2,2'-diyI-hydrogenphosphat Salze. Scheme 8. High enantioselective transfer hydrogenation. Further examples of various 3,3'-bis (2,4 l 6-triisopropylphenyl) -1, 1 '-binaphthyl-2,2'-diyI-hydrogen phosphate salts.
Schema 9. Hochenantioselektive Transferhydrierung. Weitere Beispiele.Scheme 9. Highly enantioselective transfer hydrogenation. Further examples.
Diese Reaktion lässt sich auf das industriell wichtige Substrat Citral ausdehnen, welches dabei hochenantioselektiv zum Parfuminhaltsstoff Citronellal reduziert wird (Schema 10). This reaction can be extended to the industrially important substrate citral, which is highly enantioselectively reduced to the perfume substance citronellal (Scheme 10).
Citral (5) (R)-Citronellal (6) 91 % ee Schema 10. Erfindungsgemäße Hochenantioselektive Transferhydrierung von CitralCitral (5) (R) -Citronellal (6) 91% ee Scheme 10. High enantioselective transfer hydrogenation of citral according to the invention
73 % Umsatz73% sales
Schema 11. Erfindungsgemäße Hochenantioselektive Transferhydrierung eines aliphatischen Substrates Scheme 11. High enantioselective transfer hydrogenation of an aliphatic substrate according to the invention
Experimenteller TeilExperimental part
Darstellung der Salze Die Säure (1 eq) in Diethylether (2ml/mmol) wurde vorgelegt und das jeweilige Amin (1 eq) in einer Portion zugegeben. Nach 2 bis 15 Stunden rühren bei Raumtemperatur wurde das entstandene Salz abfiltriert oder das Lösungsmittel am Rotationsverdampfer abgedampft. Die Salze wurden in quantitativen Ausbeuten erhalten.Preparation of the salts The acid (1 eq) in diethyl ether (2 ml / mmol) was initially charged and the respective amine (1 eq) was added in one portion. After stirring for 2 to 15 hours at room temperature, the resulting salt was filtered off or the solvent was evaporated on a rotary evaporator. The salts were obtained in quantitative yields.
Asymmetrische TransferhydrierungAsymmetric transfer hydrogenation
Der Aldehyd (2a-f) (1 eq) und Katalysator (1a-1w) (0.2 eq für 1a, bzw. 0.1 eq für 1b-1w) wurden in THF (aliphatische Substrate) oder 1 ,4-Dioxan (aromatische Substrate) (10 ml/mmol) vorgelegt und für 2-5 min bei Raumtemperatur (aliphatische Substrate) oder 500C (aromatische Substrate) gerührt. Im Anschluss wurde Hantzsch Ester (4 oder 5) zugegeben und für weiter 24 Stunden gerührt. Die Reaktionsmischung wurde mit Wasser (40 ml/mmol) aufgefüllt und mit Diethylether (aliphatische Substrate) oder Methylenchlorid (aromatische Substrate) (3 x 40ml/mmol) extrahiert. Die vereinigten organischen Phasen wurden über Magnesiumsulfat getrocknet und am Rotationsverdampfer eingeengt. Säulenchromatographie (Pentan/Diethylether oder Hexan/Essigester) ergab die Produkte in der angegebenen Ausbeuten und Enantiomerenüberschüssen.The aldehyde (2a-f) (1 eq) and catalyst (1a-1w) (0.2 eq for 1a, and 0.1 eq for 1b-1w, respectively) were prepared in THF (aliphatic substrates) or 1, 4-dioxane (aromatic substrates) (10 ml / mmol) and stirred for 2-5 min at room temperature (aliphatic substrates) or 50 0 C (aromatic substrates). Subsequently, Hantzsch ester (4 or 5) was added and stirred for a further 24 hours. The reaction mixture was washed with water (40 ml / mmol) and extracted with diethyl ether (aliphatic substrates) or methylene chloride (aromatic substrates) (3 x 40ml / mmol). The combined organic phases were dried over magnesium sulfate and concentrated on a rotary evaporator. Column chromatography (pentane / diethyl ether or hexane / ethyl acetate) gave the products in the indicated yields and enantiomeric excesses.
Für die in Schema 7-9 und 11 aufgeführten Beispiele wurde eine Probe entnommen und der Umsatz mittels NMR bestimmt.For the examples given in Schemes 7-9 and 11, a sample was taken and the conversion determined by NMR.
Asymmetrische Transferhydrierung von α,ß-ungesättigten Ketonen (neues Kapitel)Asymmetric Transfer Hydrogenation of α, ß-Unsaturated Ketones (new chapter)
Das Verfahren lässt sich auch auf α,ß-ungesättigte Ketone Anwenden. Insbesondere chirale Phosphat Salze primärer Aminosäurester haben sich als leistungsfähige und hoch enantioselektive Katalysatoren erwiesen.The method can also be applied to α, β-unsaturated ketones. In particular, chiral phosphate salts of primary amino acid esters have proven to be powerful and highly enantioselective catalysts.
So katalysiert das Salz 7a in Gegenwart des Hantzsch esters 8, die hochenantioselektive Transferhydrierung verschiedener alpha, beta-ungesättigter Ketone (9) (Schema 12). Weitere katalytische Salze für die enantioselektive Transferhydrierung sind in den Schemen 13-15 gezeigt.For example, salt 7a catalyzes the highly enantioselective transfer hydrogenation of various alpha, beta-unsaturated ketones (9) in the presence of Hantzsch ester 8 (Scheme 12). Additional catalytic salts for the enantioselective transfer hydrogenation are shown in Schemes 13-15.
Schema 12. Erfindungsgemäße Hochenantioselektive Transferhydrierungen. Scheme 12. High enantioselective transfer hydrogenations according to the invention.
Schema 13. Hochenantioselektive Transferhydrierung. Weitere Beispiele vom terf-Butyl Valinate-Salzen. Scheme 13. Highly enantioselective transfer hydrogenation. Further examples of terf-butyl valinate salts.
Schema 14. Hochenantioselektive Transferhydrierung. Weitere Beispiele diverser 3,3'-Bis(2,4,6-triisopropy!phenyl)-1 ,1'-binaphthyl-2,2'-diyl-hydrogenphosphat Salze. Scheme 14. Highly enantioselective transfer hydrogenation. Further examples of various 3,3'-bis (2,4,6-triisopropylphenyl) -1, 1'-binaphthyl-2,2'-diyl hydrogen phosphate salts.
Schema 15. Hochenantioselektive Transferhydrierung. Beispiele des „matched/mismatched" Effektes.Scheme 15. Highly enantioselective transfer hydrogenation. Examples of the "matched / mismatched" effect.
Experimenteller TeilExperimental part
Darstellung der SalzeRepresentation of the salts
Die Säure (1 eq) in Diethylether (2ml/mmol) wurde vorgelegt und das jeweilige primäre Amin (1 eq) in einer Portion zugegeben. Nach 2 bis 15 Stunden rühren bei Raumtemperatur wurde das entstandene Salz abfiltriert oder das Lösungsmittel am Rotationsverdampfer abgedampft. Die Salze wurden in quantitativen Ausbeuten erhalten.The acid (1 eq) in diethyl ether (2 ml / mmol) was initially charged and the respective primary amine (1 eq) was added in one portion. After stirring for 2 to 15 hours at room temperature, the resulting salt was filtered off or the solvent was evaporated on a rotary evaporator. The salts were obtained in quantitative yields.
Asymmetrische Transferhydrierung Das Keton (9a-l) (1 eq) und Katalysator (7a-s) (0.1 eq für 9a-c, bzw. 0.05 eq für 9d-l) wurden in Bu2O (0,33 ml/mmol) vorgelegt und für 2-5 min bei 6O0C gerührt. Im Anschluss wurde Hantzsch Ester (8) (1.2 eq) zugegeben und für weiter 48 Stunden gerührt; Die Reaktionsmischung wurde mit Natriumlauge (2N, 40 ml/mmol) aufgefüllt und mit Diethylether (3 x 40ml/mmol) extrahiert. Die vereinigten organischen Phasen wurden über Magnesiumsulfat getrocknet und am Rotationsverdampfer eingeengt. Säulenchromatographie (Pentan/Diethylether) ergab die Produkte in der angegebenen Ausbeuten und Enantiomerenüberschüssen.Asymmetric transfer hydrogenation The ketone (9a-l) (1 eq) and catalyst (7a-s) (0.1 eq for 9a-c, and 0.05 eq for 9d-l, respectively) were dissolved in Bu 2 O (0.33 ml / mmol). and stirred for 2-5 min at 6O 0 C stirred. In connection Hantzsch ester (8) (1.2 eq) was added and stirred for a further 48 hours; The reaction mixture was made up with sodium hydroxide solution (2N, 40 ml / mmol) and extracted with diethyl ether (3 × 40 ml / mmol). The combined organic phases were dried over magnesium sulfate and concentrated on a rotary evaporator. Column chromatography (pentane / diethyl ether) gave the products in the indicated yields and enantiomeric excesses.
Für die flüchtigen gesättigten Ketone, sowie für die in Schema 13-15 aufgeführten Beispiele wurde eine Probe entnommen und der Umsatz mittels GC bestimmt.For the volatile saturated ketones, as well as for the examples given in Scheme 13-15, a sample was taken and the conversion was determined by GC.
Asymmetrische EpoxidierungAsymmetric epoxidation
Entsprechend Schema 2 können auch Epoxidierungen auf analoge weise katalysiert werden. So kann man z.B. Zimtaldehyd mit tert-Butylhydroperoxid enantioselektiv in das entsprechende Epoxid umwandeln wenn als Katalysatoren die Salze 11bw verwendet wird (Schema 16) According to Scheme 2 also epoxidations can be catalyzed in an analogous manner. For example, cinnamaldehyde can be enantioselectively converted into the corresponding epoxide with tert-butyl hydroperoxide if the catalysts 11bw are used (Scheme 16).
Schema 17. Hochenantioselektive Epoxidierung. Weitere Beispiele diverser 3,3'-Bis(2,4,6-triisopropylphenyl)-1 ,1 '-binaphthyl-2,2'-diyl-hydrogenphosphat Salze mit kommerziellen achiralen Aminen Scheme 17. High enantioselective epoxidation. Further examples of various 3,3'-bis (2,4,6-triisopropylphenyl) -1, 1'-binaphthyl-2,2'-diyl hydrogen phosphate salts with commercial achiral amines
Schema 18. Hochenantioselektive Epoxidierung. Weitere Beispiele diverser 3,3'-Bis(2,4]6-triisopropylphenyl)-1 ,1'-binaphthyl-2,2'-diyl-hydrogenphosphat Salze mit chiralen Aminen Scheme 18. High enantioselective epoxidation. Further examples of various 3,3'-bis (2,4 ] 6-triisopropylphenyl) -1, 1'-binaphthyl-2,2'-diyl hydrogen phosphate salts with chiral amines
Schema 19. Hocheπantioselektive Epoxidierung. Weitere Beispiele diverser . 3,3'-Bis(2,4,6-triisopropylphenyl)-1 ,1'-binaphthyl-2,2'-diyl-hydrogenphosphat Salze mit Benzoesäure Hydrazide Scheme 19. Highly enantioselective epoxidation. Further examples of various. 3,3'-Bis (2,4,6-triisopropylphenyl) -1, 1'-binaphthyl-2,2'-diyl hydrogen phosphate salts with benzoic acid hydrazides
Schema 20. Hochenantioselektive Epoxidierung. Weitere Beispiele diverser 3,3'-Bis(2,4,6-triisopropylphenyl)-1 ,1'-binaphthyl-2,2'-diyl-hydrogenphosphat Salze mit Dibenzylaminen Scheme 20. High enantioselective epoxidation. Further examples of various 3,3'-bis (2,4,6-triisopropylphenyl) -1, 1'-binaphthyl-2,2'-diyl hydrogen phosphate salts with dibenzylamines
Schema 21. Hochenantioselektive Epoxidierung. Weitere Beispiele diverser Dibenzylamin Salze Scheme 21. High enantioselective epoxidation. Further examples of various dibenzylamine salts
Schema 22. Hochenantioselektive Epoxidierung. Weitere Beispiele diverser Bis(3,5-bis(trifluoromethyl)benzyl)amin Salze Scheme 22. High enantioselective epoxidation. Further examples of various bis (3,5-bis (trifluoromethyl) benzyl) amine salts
11bw11bw
Experimentelle Vorschrift: Zimtaldehyd (1 mmol) in Dioxan (4mL) wird mit dem Katalysator (0.1 mmol, 10 mol%) und t- BuOOH (1.1 mmol, 1.1 eq) versetzt und die Reaktionsmischung wird bei 35°C für 3d gerührt. Die Reaktionsmischung wurde mit einer 10%iger NaHSO3 Lösung (4 ml) aufgefüllt und mit Diethylether (3 x 4 ml) extrahiert. Die vereinigten organischen Phasen wurden über Magnesiumsulfat getrocknet und am Rotationsverdampfer eingeengt. Säulenchromatographie liefert das reine Epoxid in den angegebenen Ausbeuten und ee's (Schema 8).Experimental procedure: Cinnamaldehyde (1 mmol) in dioxane (4 mL) is treated with the catalyst (0.1 mmol, 10 mol%) and t-BuOOH (1.1 mmol, 1.1 eq) and the reaction mixture is stirred at 35 ° C for 3d. The reaction mixture was made up with a 10% NaHSO 3 solution (4 ml) and extracted with diethyl ether (3 x 4 ml). The combined organic phases were dried over magnesium sulfate and concentrated on a rotary evaporator. Column chromatography yields the pure epoxide in the indicated yields and ee's (Scheme 8).
Asymmetrische Acyl-Transferreaktion Entsprechend Schema 3 kann die neue Katalysestrategie mit chiralen Anionen auch auf Acyltransferreaktionen ausgedehnt werden. Umsetzung von a-phenylethanol mit Acetanhydrid in Gegenwart der Salze 9 und 10 findet mit eindeutig messbarer Enantioselektivität statt (Schema 13).Asymmetric acyl transfer reaction According to Scheme 3, the new catalytic strategy with chiral anions can also be extended to acyl transfer reactions. Reaction of a-phenylethanol with acetic anhydride in the presence of salts 9 and 10 takes place with clearly measurable enantioselectivity (Scheme 13).
45% Umsatz, 8.4/13.5% ee (Alkohol/Ester) 39% Umsatz, 10.4/22.6% ee (Alkohol/Ester)45% conversion, 8.4 / 13.5% ee (alcohol / ester) 39% conversion, 10.4 / 22.6% ee (alcohol / ester)
Schema 24. Erfindungsgemäße enantioselektive Veresterung Experimentelle Vorschrift:Scheme 24. Enantioselective esterification of the invention. Experimental protocol:
Die Verwendung von Salz 16 ist exemplarisch. So wird die chirale Phosphorsäure (TRIP, 7.53 mg, 0.01 mmol) und DMAP (1.22 mg, 0.01 mmol) in Toluol (1 ml_) für eine Stunde gerührt. Anschließend wird der racemische Alkohol (0.1 mmol) sowie Ac2O (0.05 mmol, 0.5 eq) hinzu gegeben. Nach angegebenem Umsatz wird das Produkt via wäßriger Aufarbeitung isoliert. The use of salt 16 is exemplary. Thus, the chiral phosphoric acid (TRIP, 7.53 mg, 0.01 mmol) and DMAP (1.22 mg, 0.01 mmol) in toluene (1 ml) are stirred for one hour. Then the racemic alcohol (0.1 mmol) and Ac 2 O (0.05 mmol, 0.5 eq) are added. After specified conversion, the product is isolated via aqueous workup.

Claims

Patentansprüche claims
1. Verfahren zur Herstellung von chiralen organischen Verbindungen durch asymmetrische Katalyse, wobei ionische Katalysatoren eingesetzt werden, dadurch gekennzeichnet, dass das Katalysatoranion des ionischen Katalysators chiral ist.1. A process for the preparation of chiral organic compounds by asymmetric catalysis, wherein ionic catalysts are used, characterized in that the catalyst anion of the ionic catalyst is chiral.
2. Verfahren nach Anspruch 1 , dadurch gekennzeichnet, dass die Reaktion ausgewählt ist aus Reaktionen die über kationische Zwischenstufen verlaufen, wie über Imniumionen in Diels-Alder-Reaktionen, 1 ,3-dipolare Cycloadditionen, konjugierten Addtionen, Epoxidierungen, Cyclopropanierungen, Transferhydrierungen, Mukaiyama- Michael-Additionen, Knoevenagel-Reaktionen, oder über Acylpyridiniumionen wie in Acyltransferreaktionen.2. The method according to claim 1, characterized in that the reaction is selected from reactions which proceed via cationic intermediates, such as on Imniumionen in Diels-Alder reactions, 1, 3-dipolar cycloadditions, conjugate Addtionen, epoxidations, cyclopropanations, transfer hydrogenations, Mukaiyama - Michael additions, Knoevenagel reactions, or via acylpyridinium ions as in acyl transfer reactions.
3. Verfahren nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass das Katalysatoranion ausgewählt ist aus chiralen organischen Phosphaten, Sulfonaten,3. The method according to claim 1 or 2, characterized in that the catalyst anion is selected from chiral organic phosphates, sulfonates,
Sulfaten, Carboxylaten, Imiden, Sulfonylimiden etc.Sulfates, carboxylates, imides, sulfonylimides, etc.
4. Verfahren nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass das Anion sich von Binaphtol ableitet.4. The method according to any one of claims 1 to 3, characterized in that the anion is derived from binaphtol.
5. Verfahren nach einem der Anspruch 1 bis 4, dadurch gekennzeichnet, dass das Anion ausgewählt ist aus5. The method according to any one of claims 1 to 4, characterized in that the anion is selected from
worin wherein
R Wasserstoff, substituiertes oder unsubstituiertes Alkyl oder substituiertes oder unsubstituiertes Aryl bedeutet. R is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aryl.
6. Verfahren nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass das Kation eine Ammoniumverbindung ist. 6. The method according to any one of claims 1 to 5, characterized in that the cation is an ammonium compound.
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US7683191B2 (en) 2010-03-23
WO2007098741A3 (en) 2007-10-18
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