EP1381583A1

EP1381583A1 - Polymer-bound catalyst for the enantioselective cleavage of pro-chiral anhydrides

Info

Publication number: EP1381583A1
Application number: EP02706770A
Authority: EP
Inventors: Jens WÖLTINGER; Hans-Peter Krimmer; Dietmar Reichert; Juan Jose Almena Perea; Karlheinz Drauz; Andreas Karau
Original assignee: Degussa GmbH
Current assignee: Evonik Operations GmbH
Priority date: 2001-04-26
Filing date: 2002-03-20
Publication date: 2004-01-21
Also published as: WO2002088047A1; US20040204606A1; JP2004527555A

Abstract

The invention relates to the use of catalysts comprising the structures of general formulas (I), (II) or (III), for the asymmetric cleavage of anhydrides.

Description

Polymer-bound catalyst for the enantioselective opening of prochiral anhydrides

The present invention is directed to the use of optically active polymer enlarged catalysts. In particular, the invention is concerned with polymer-enlarged catalysts which have one or more structures of the general formula (I) or (II) as the active unit which determines the chiral induction.

DHQ (I) DHQD (II)

Homogeneously soluble polymer-enlarged chiral catalysts are important tools for the synthesis of enantiomerically enriched organic compounds, especially on an industrial scale, because on the one hand they help to produce the desired products in an extremely cost-effective manner due to their catalytic activity and the ability to recycle and reuse them. In addition, the reactions carried out with them do not show the phase change of the substrate and product which is inherent in the reaction for heterogeneously soluble polymer-enlarged catalysts. There is still a need for catalysts for use in the organic catalytic synthesis of chiral compounds. Janda and Bolm et al. reported on the recently synthesized representatives of the quinine / quinidine ligands (Chem. Co mun. 1999, 1917-1924; Eur. J. Org. Che. 1988, 21-27).

In the field of the enantioselective dihydroxylation reaction according to Sharpless, homogeneously soluble polymer-enlarged quinine / quinidine ligands are already known (J. Am. Chem. Soc. 1996, 118, 7632; Tetrahedron Lett. 1997, 38, 1527; Angew. Chem ., Int. Ed. Engl. 1997, 36, 773).

It is also known to use quinine / quinidine ligands as catalysts in the enantioselective opening of prochiral anhydrides (Deng et al., J. Am. Chem. Soc. 2000, 9542; Bolm et al., Synlett, 1999, 2, 195-196 ).

The object of the present invention was therefore to specify further uses for homogeneously soluble polymer-enlarged catalysts of the quinine / quinidine type for the asymmetric synthesis of organic compounds.

This object is achieved by the use of the catalysts having the features of claim 1. Claims 2 to 6 protect particular embodiments of the use according to the invention.

The fact that, in a process for the asymmetrical opening of prochiral anhydrides, optically active homogeneously soluble polymer-enlarged catalysts comprising one or more structures of the general formula (I), (II) or (III) as the active unit which determines the chiral induction

DHQ (I) DHQD (II),

used where

R ¹ , R ² independently of one another are H, (-CC ₈ ) -alkyl,

(C_-C ₈ ) acyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -Cι ₈ ) aryl, (C ₇ -C_ ₉ ) aralkyl, (C ₃ -Cι ₈ ) heteroaryl, ( C ₄ -C ₁₉ ) heteroaralkyl, ((Ci-C ₈ ) alkyl) ι_ ₃ - (C ₃ -C ₈ ) cycloalkyl, ((C_-C ₈ ) alkyl) __ ₃ - (C ₆ -C ₁₈ ) - Aryl, ((-C ₈ -C ₈ ) alkyl) _- ₃ - (C ₃ -C ₈ ) heteroaryl, R ³ is H, or R ¹ , R ² or R ³ is the link to the polymer enlargement fication,

R ⁴ = DHQ (I) or DHQD (II) and R ^{5 is} H or the linkage to a polymer, the desired optically enriched compounds are obtained in very excellent yields and with high enantiomeric excesses. The catalysts are very easy to separate from the low molecular weight compounds by means of the polymer bond, for example by filtration, and are therefore accessible to the extremely simple, but no less advantageous, recycling desired by the invention.

Polymer enlargement:

The polymer enlargement can be chosen freely within the scope of the invention. It is limited on the one hand by practicality and cost considerations, and on the other hand by technical framework conditions (retention, solubility, etc.). Some polymer enlargements for catalysts are known from the prior art (Reetz et al., Angew. Chem. 1997, 109, 1559f .; Seebach et al., Helv. Chim Acta 1996, 79,

1710f ~.; Kragl et al., Angew. Chem. 1996, 108, 684f. _; Schurig et al., Chem. Ber./Recueil 1997, 130, 879f .; Bolm et al., Angew. Chem. 1997, 109, 773f .; Bolm et al. Eur. J. Org. Chem. 1998, 21f .; Baystone et al. in Specialty Chemicals 224f .; Salvadori et al., Tetrahedron: Asymmetry 1998, 9, 1479; Wandrey et al. , Tetrahedron: Asymmetry 1997, 8, 1529f .; ibid. 1997, 8, 1975f .; Togni et al. J. Am. Chem. Soc. 1998, 120, 10274f., Salvadori et al. , Tetrahedron Lett. 1996, 37, 3375f; WO 98/22415; in particular DE 19910691.6; Janda et al., J. Am. Chem. Soc. 1998, 120,

9481f .; Andersson et al., Chem. Commun. 1996, 1135f .; Janda et al., Soluble Polymers 1999, 1, 1; Janda et al., Chem. Rev. 1997, 97, 489; Geckler et al., Adv. Polym. Be. 1995, 121, 31; White et al., In "The Chemistry of Organic Silicon Compounds" Wiley, Chichester, 1989, 1289; Schuberth et al., Macromol. Rapid Commun. 1998, 19, 309; Sharma et al., Synthesis 1997, 1217; "Functional Polymers" Ed .: R. Arshady, ASC, Washington, 1996; "Internship of Macromolecular Substances", D. Braun et al., VCH-Wiley, Weinheim 1999). The polymer enlargement is furthermore preferably formed by polyacrylates, polyacrylamides, polyvinylpyrrolidinones, polysiloxanes, polybutadienes, polyisoprenes, polyalkanes, polystyrenes, polyoxazolines or polyethers or mixtures thereof. In a very particularly preferred embodiment, polystyrenes are used to build up the polymer enlargement.

Left:

A linker can be installed between the actual active unit and the polymer enlargement. The linker serves to build up a distance between the active unit and the polymer in order to reduce or eliminate mutual interactions which are disadvantageous for the reaction. In principle, the linkers can be freely chosen by the person skilled in the art. They are to be selected based on how well they are coupled to the polymer / monomer on the one hand and to the active center on the other. Suitable linkers can be found, inter alia, in the references mentioned above under the heading polymer enlargement. In _. Within the scope of the invention, these active units of the formulas (I) to (III) are advantageously selected directly or preferably via a linker from the group a) -Si (R ₂ ) - b) - (SiR ₂ -0) _n - n = l-10000 c) - (CHR-CHR-O) _n - n = l-10000 d) - (X) n- n = l-20 e) Z- (X) _n - n = 0-20 f) - (X) _n -W n = 0-20 g) Z- (X) _n -W n = 0-20 where

R means H, (-C ₈ -C) alkyl, (C ₆ -C ₈ ) aryl, (C ₇ -C ₁₉ ) aralkyl, ((-C ₈ ) alkyl) i- ₃ - (Ce- Cis) aryl,

X denotes (C ₆ -C ₈ ) arylene, (C_ C ₈ ) alkylene, (C_ C ₈ ) alkenylene, ((C_ C ₈ ) alkyl) _! _ ₃ - (C ₆ -C_ ₈ ) arylene, (C ₇ -C_ ₉ j - aralkylene, Z, W independently of one another mean -C (= 0) 0-,

-C (= 0) NH-, -C (= 0) -, NR, 0, CHR, CH ₂ , C = S, S, PR, bound to the polymer enlargement.

Further preferred compounds that can be used as linkers are shown in the following scheme:

However, linkers such as e.g. B. 1, 4 '-biphenyl, 1,2-ethylene, 1, 3-propylene, PEG- (2-10), α, ω-siloxanylene or 1,4-phenylene and, ω-l, 4-bisethylene benzene or Linkers which, starting from siloxanes of the general formula IV

R: Me, Et n = 0-10

are available. Under hydrosilylation conditions (overview of the hydrosilylation reaction by Ojima in The Chemistry of Organic Silicon Compounds, 1989 John Wiley & Sons Ltd., 1480-1526) they can easily be linked to any double bonds present in the polymers and suitable functional groups of the active centers tie.

The size of the polymer enlargement should be such that the catalyst dissolves in the solvent to be used, so that one can work in a homogeneous phase. The catalyst used is therefore preferably a homogeneously soluble one. This avoids negative effects that occur due to the phase changes of the substrates and products that would otherwise be necessary when using heterogeneous catalysts.

The polymer-enlarged catalysts can have an average molecular weight in the range from 1,000 to 1,000,000, preferably 5,000 to 500,000, particularly preferably 5,000 to 300,000, g / mol.

It is within the scope of the invention that according to the

A person skilled in the art knows that the above-mentioned constituents of the polymer-enlarged catalysts (I) to (III) (polymer, linker, active center / unit) can be combined in any way with regard to optimal reaction control.

Combination of polymer enlargement to linker / active unit:

In principle there are two approaches how the linker / active unit can be attached to the polymer enlargement: a) the active unit causing the chiral induction is bound with a linked linker or directly to a monomer and this is copolymerized with further unmodified monomers, or b) the active unit causing the chiral induction is linked via a linker or directly to the finished polymer , Possibly. polymers can be prepared according to a) or b) and these can be block copolymerized with other polymers which also have the active units which determine the chiral induction or which do not have them.

In principle, the same applies to the number of linker / active units per monomer in the polymer that as many such catalytically active units as possible should fit on one polymer, so that the conversion per polymer is increased as a result. On the other hand, however, the units should be at such a distance from one another that a mutual negative influence on the reactivity (TOF, selectivity) is minimized or does not take place at all. The distance between the linker / active centers in the polymer should therefore preferably be in the range of 1-200 monomer units, preferably 5-25 monomer units.

In an advantageous embodiment, such sites in the polymer or monomer to be polymerized are used

Connection of the linker / active unit used, which. can be easily functionalized or allow existing functionality to be used for connection. For example, heteroatoms or unsaturated carbon atoms are preferred for establishing the bond.

For example, in the case of styrene / polystyrene, the aromatics present can be used as connection points to the linkers / active centers. Functionalities can be added to these aromatics, preferably in the 3-, 4-, 5-position, particularly preferably the 4- position, via normal aromatic chemistry to be well connected. However, it is also advantageous to add, for example, already functionalized monomer to the mixture to be polymerized and, after the polymerization, to bind the linker to the functionalities present in the polystyrene. For example, para-hydroxy, para-chloromethyl or para-aminostyrene oil derivatives are advantageously suitable for this purpose.

In the case of the polyacrylates, there is one acid group or ester group in the monomer constituent, to which the linker or the active unit can be attached before or after the polymerization, preferably via an ester or amide bond.

Polysiloxanes as a polymer enlargement are preferably constructed in such a way that hydromethylsilane units are also present in addition to dimethylsilane units. At these points, the linker / active units can then still be coupled via hydrosilylation. These can preferably be linked to the functionalities envisaged in the polymer under hydrosilylation conditions (overview of the hydrosilylation reaction by Ojima in The Chemistry of Organic Silicon Compounds, 1989 John Wiley & Sons Ltd., 1480-1526).

Suitable polysiloxanes modified in this way are known in the literature ("Siloxane polymers and copolymers", White et al., In Ed. S. Patai "The Chemistry of Organic Silicon Compounds" Wiley, Chichester, 1989, 46, 2954; C. Wandrey et al. TH: Asymmetry 1997, 8, 1975).

Combination of linker to active unit:

What applies to the connection of polymer to linker / active unit is synonymous with the connection of the active center (active unit) to the linker.

The linker connection to the active units can thus preferably take place via heteroatoms or certain functionalities such as C = 0, CH ₂ , 0, N, S, P, Si, B, preferably E- ether / thioether bonds, amine bonds, amide bonds are formed or esterifications, alkylations, silylations and additions to double bonds are carried out.

Particularly preferred are those connection options which have already been described in the prior art for the polymer enlargement of the monomeric active units (WO98 / 35927; Chem. Commun. 1999, 1917; Angew. Chem. 1997, 16, 1835; J. Am. Chem. Soc. 1996, 118, 7632; Tetrahedron Lett. 1997, 38, 1527; Eur. J. Org. Chem. 1998, 21; Angew. Chem. 1997, 109, 773; Chem. Commun. 1997, 2353; Tetrahedron: Asymmetry 1995, 6, 2687; ibid 1993, 4, 2351; Tetrahedron Lett. 1995, 36, 1549; Synlett 1999, 8, 1181; Tetrahedron: Asymmetry 1996, 7, 645; Tetrahedron Lett. 1992, 33, 5453; ibid 1994 , 35, 6559; Tetrahedron 1994, 50, 11321; Chirality 1999, 11, 745; Tetrahedron Lett. 1991, 32, 5175; Tetrahedron Lett. 1990, 31, 3003; Chem. Commun. 1998, 2435; Tetrahedron Lett. 1997, 38, 2577).

In principle, a polymer-enlarged catalyst for the purpose of the invention can also be produced according to the specification in DE10029600.

The active units are preferably linked to the polymers / linkers via the following groups of compounds.

The definitions given above apply to the radicals R ⁴ and R ⁵ . The structures shown can advantageously be linked to the polymer / linker via the R ⁵ radicals, at least one of the stated connection possibilities per connection being realized.

The catalysts under consideration are particularly preferably used for the asymmetrical opening of prochiral anhydrides, the process being carried out in a membrane reactor. The continuous mode of operation which is possible in this apparatus in addition to the batch and semi-continuous mode of operation can, as desired, be carried out in cross-flow filtration mode (FIG. 2) or as dead-end filtration (FIG. 1). In principle, both process variants are described in the prior art (Engineering Processes for Bioseparations, Ed.: L.R. Weatherley, Heinemann, 1994, 135-165; Wandrey et al., Tetrahedron Asymmetry 1999, 10, 923-928).

The use of the present invention is particularly preferred in such a way that the reaction is operated in repetitive batch mode and the catalyst is washed in the membrane reactor between the reactions. Repetitive batch means carrying out the reaction several times in succession, with the reactants initially being fed to the reactor and, after the reaction has ended, the products being drawn off before the reactor is charged again. The catalyst remaining in the reactor is washed before the reactants are fed into the reactor. It has the task of removing reaction residues such as product, starting material and the like still adhering in the reactor from the reactor in order to be able to assume equally good starting conditions. It has been shown that the products are partially bound by the catalyst (eg acid-base pair). The washing can therefore preferably also serve this purpose and can be carried out in such a way that no product molecule in the reactor remains mixed or physically bound. On the other hand, however, it is also possible to operate this reaction of the anhydrides with the catalyst under conditions which help to prevent a reaction of the product with the catalyst. For example, the fact that further bases are added to the reaction in order to suppress the acid-base reaction of the products with the catalyst should be regarded as such.

In order for a catalyst to appear suitable for use in a membrane reactor, it has to meet a wide variety of criteria. On the one hand, care must be taken to ensure that there is a correspondingly high retention capacity for the polymer-enlarged catalyst so that there is satisfactory activity in the reactor over a desired period of time without the catalyst having to be replenished continuously, which is disadvantageous in economic terms (DE19910691 ). Furthermore, the catalyst used should have an appropriate tof (turn over frequency) in order to be able to convert the substrate into the product in economically reasonable periods of time. The catalysts of the quinine / quinidine type known from the prior art with reaction rates in the period of 2 h and ee values of 85% could be optimized for use in the membrane reactor to reaction rates of 15 minutes and> 90% ee. For this purpose, the catalyst must be used in a 10-fold excess over the anhydride. The concept of in-situ recycling of the catalyst using a membrane reactor enables economical operation despite the high use of catalysts. Preparation of a polymer enlarged (DHQ) ₂ AQN catalyst can look as follows.

The following reaction was carried out with this catalyst in the Menbran reactor in repetitive batch mode.

Conditions: repetitive batch in the dead-end apparatus (FIG. 1) with 10 ml of toluene, 025 mmol of anhydride, 2.5 mmol of methanol per batch and a total of 0.25 mmol of catalyst

The result is shown in Fig. 3. It can be seen that an almost quantitative yield is achieved in terms of sales. However, the ee value drops dramatically after a short time. By washing the catalyst one or more times in the membrane reactor between the individual runs, e.g. with a solution of toluene and methanol (10 eq. Methanol based on the anhydride used) and then one or more times with pure toluene, the ee value can be achieved with the same good conversion be kept constant at about 60%. However, an NMR protocol of the catalyst used subsequently showed that 2 eq. Product was present, suggesting that the product (acid) appears to be bound to the catalyst (base). This could be the reason that the ee value is not as good as that shown by the monomeric ligand, since the monomeric ligand is used only once and thus formation of the acid-base pair cannot influence the selectivity. This is also clear when using the molecular weight-increased catalyst 3, since here too, selectivity comparable to the monomeric catalyst is achieved in the first batch. Only the further use of the catalyst leads to a reduction in selectivity through the formation of the product-catalyst pair. This complex can be broken up by suitable protocols for washing the catalyst between the batch experiments in a repetitive batch, and the selectivity can be increased. (Fig.3). However, the principle of implementing this reaction in the membrane reactor has been impressively demonstrated.

In the context of the invention, mixtures of polymer-enlarged polymers are understood to mean the fact that individual polymers of different provenance are polymerized together to form block polymers. Statistical mixtures of the monomers in the polymer are also possible.

In the context of the invention, polymer enlargement is understood to mean the fact that one or more active units which are responsible for the chiral induction are copolymerized in a suitable form with further monomers, or that these units are coupled to an already existing polymer by methods known to the person skilled in the art. Forms of the units suitable for copolymerization are well known to the person skilled in the art and can be freely selected by him. The preferred procedure is to derivatize the molecule under consideration, depending on the type of copolymerization, with groups capable of copolymerization, e.g. in copolymerization with (meth) acrylates by coupling to acrylate molecules.

As (Ci-C _ß ) alkyl are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl together with all binding isomers. A (CÖ-C _I S) aryl radical is understood to mean an aromatic radical with 6 to 18 C atoms. In particular, these include compounds such as phenyl, naphthyl, anthryl, phenanthryl, biphenyl radicals. These can be substituted one or more times with (-C ₈ -C) alkoxy., (-C ₈ -C) haloalkyl, OH, Cl, NH ₂ , N0 ₂ . In addition, the rest can have one or more heteroatoms such as N, 0, S.

(Ci-Cβ) alkoxy is a (Cι-C ₈ ) alkyl radical bonded to the molecule under consideration via an oxygen atom.

A (C ₇ -C ₉ ) aralkyl radical is a via a (C_-C ₈ ) -

Alkyl residue bound to the molecule (Cε-Cis) aryl residue.

In the context of the invention, the term acrylate is also understood to mean the term methacrylate.

(CI ~ CR) -haloalkyl is a (C_-C ₈ ) -alkyl radical substituted with one or more halogen atoms. Halogen and fluorine are particularly suitable as halogen atoms.

On . In the context of the invention, (C ₃ -C ₈ ) heteroaryl radical denotes a five-, six- or seven-membered aromatic ring system of 3 to 18 carbon atoms, which heteroatoms such as, for. B. has nitrogen, oxygen or sulfur in the ring. Such heteroaromatics are in particular radicals, such as 1-, 2-, 3-furyl, such as 1-, 2-, 3-pyrrolyl, 1-, 2-, 3-thienyl, 2-, 3-, 4-pyridyl, 2-, 3-, 4-, 5-, 6-, 7-indolyl, 3-, 4-, 5-pyrazolyl, 2-, 4-, 5-imidazolyl, acridinyl, quinolinyl, phenanthridinyl, 2-, 4-, 5-,

6-pyrimidinyl. This can be substituted one or more times with (-CC ₈ ) alkoxy, (-CC ₈ ) haloalkyl, OH, halogen, NH ₂ , NO ₂ , SH, S- (-C ₈ ) -alkyl.

A (C ₄ -C 1 ₉₎ -heteroaralkyl the (C ₇ -C ₁ 9) -aralkyl corresponding heteroaromatic system is understood. The term (C_-C ₈ ) alkylene chain is to be understood as a (C)-C ₈ ) alkyl radical which is bonded to the molecule in question via two different C atoms. This can be substituted one or more times with (-CC ₈ ) alkoxy, (-CC ₈ ) haloalkyl, OH, halogen, NH _{2 /} NO ₂ , SH, S- (C ₈ -C ₈ ) alkyl.

(C ₃ -C ₈ ) Cycloalkyl means cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl or cycloocytyl radicals.

Halogen is fluorine, chlorine, bromine, iodine.

In the context of the invention, membrane reactor is understood to mean any reaction vessel in which the catalyst is enclosed in a reactor while low-molecular substances are fed to the reactor or can leave it. The membrane can be integrated directly into the reaction space or installed outside in a separate filtration module, in which the reaction solution flows continuously or intermittently through the filtration module and the retentate is returned to the reactor. Suitable embodiments include in W098 / 22415 and in Wandrey et al. in yearbook 1998, process engineering and chemical engineering, VDI p. 151ff .; Wandrey et al. in Applied Homogeneous Catalysis with Organometallic Compounds, Vol. 2, VCH 1996, pp. 832 ff .; Kragl et al. , Appl. Chem. 1996, 6, 684f. described.

The chemical structures shown relate to all possible stereoisomers that can be achieved by changing the configuration of the individual chiral centers, axes or planes, ie all possible diastereomers, as well as all optical isomers (enantiomers) that fall under them. However, it should be clarified that all active units present according to the invention should be of the same chirality within a polymer-enlarged catalyst. Descriptions of the drawings:

1 shows a membrane reactor with dead-end filtration. The substrate 1 is transferred via a pump 2 into the reactor space 3, which has a membrane 5. In addition to the solvent, the stirrer-operated reactor space contains the catalyst 4, the product 6 and unreacted substrate 1. The low molecular weight 6 is mainly filtered through the membrane 5.

Fig. 2 shows a membrane reactor with cross-flow filtration. The substrate 7 is transferred here via the pump 8 into the stirred reactor space, in which the solvent, catalyst 9 and product 14 are also located. A solvent flow is set via the pump 16, which leads into the cross-flow filtration cell 15 via a heat exchanger 12 which may be present. Here the low molecular weight product 14 is separated off via the membrane 13. High molecular weight catalyst 9 is then passed back into the reactor 10 with the solvent flow, if necessary again via a heat exchanger 12 and possibly via the valve 11.

Examples:

1.

81.4 mg (0.5 mmol) of cis-4-cyclohexene-1,2-dicarboxylic anhydride (95%) and 449.6 mg (DHQ) ₂ AQN catalyst (0.5 mmol) are suspended in 10 ml of toluene , A clear, homogeneous solution was obtained by adding 63.3 μl of methanol (2.5 mmol). After 15 minutes, no starting material could be detected by HPLC. The product was formed with an enantiomeric excess of 90.4%.

Second

The reaction was carried out in 10 ml of toluene. 0.25 mmol of anhydride and 2.5 mmol of methanol were used. Catalyst 3 was used as the catalyst. After the end of the reaction, the reaction solution was pressed out of the reactor via a membrane. The molecular weight-increased catalyst 3, however, remained behind the membrane. The next batch experiment was started by adding the starting materials, which were dissolved in toluene.

Claims

claims:

1. Use of optically active, homogeneously soluble, polymer-enlarged catalysts comprising, as the active unit which determines the chiral induction, one or more structures of the general formula (I), (II) or (III)

DHQ (I) DHQD (II),

wherein

R ^1, R ² are independently H, _(Cι-C8) - alkyl, (Cι-Cg) acyl, (C ₃ -C ₈₎ -cycloalkyl, (C ₆ -C_ ₈₎ -aryl, (C7 -C ₁₉₎ aralkyl, (C ₃ -Cι ₈₎ -heteroaryl, (C4-C19) - heteroaralkyl, _((Cι-C8) alkyl) __ ₃ - (C ₃ -C ₈₎ -cycloalkyl, (( C_-C ₈ ) -alkyl) _- ₃ - (C ₆ -C ₁₈ ) -aryl, ((C_-C ₈ ) -alkyl) ι_ ₃ - (C ₃ - C_s) -heteroaryl, R ³ is H, or R ¹ , R ² or R ³ is the link to the polymer enlargement,

R ⁴ = DHQ (I) or DHQD (II) and R ^{5 is} H or the bond to a polymer in a process for the asymmetric opening of prochiral anhydrides.

2. Use according to claim 1, • characterized in that the active unit which determines the chiral induction is selected via a linker from the group a) -Si (R ₂ ^' ) - b) - (SiR ₂ -0) "- n = l-10000 c) - (CHR-CHR-0) _n - n = l-10000 d) ~ (X) n- n = l-20 e) Z- (X) _n - n = 0-20 f) - (X) _n -W n = 0-20 g) Z- (X) _n -W n = 0-20 where R is H, (C_-C ₈ ) -alkyl, (C ₆ -C ₁₈ ) -aryl , (C ₇ -C_ ₉ ) aralkyl, ((C_ -C ₈ ) alkyl) 1-3- (C ₆ -C_ _e ) aryl, X means (C ₆ -Cι ₈ ) arylene, (C_- C ₈ ) alkylene, (C_-C ₈ ) alkenylene, ((C_-C ₈ ) alkyl) ₁ -3- (C ₆ -Cι ₈ ) arylene, (C7-C ₁ 9) aralkylene, Z , W independently of one another are -C (= 0) 0-,

-C (= 0) NH-, -C (= 0) -, NR, 0, CHR, CH ₂ , C = S, S, PR is bound to the polymer.

3. Use according to claim 1 and / or 2, characterized in that the polymer enlargement is formed by polyacrylates, polyacrylamides, polyvinylpyrrolidinones, polysiloxanes, polybutadienes, polyisoprenes, polyalkanes, polystyrenes, polyoxazolines or polyethers or mixtures thereof.

4. Use according to one or more of the preceding claims, characterized in that it is a homogeneously soluble catalyst.

5. Use according to one or more of the preceding claims, characterized in that the average molecular weight of the catalyst is in the range of 5,000-300,000 g / mol.

6. Use according to one or more of the preceding claims, characterized in that one carries out the asymmetrical opening of prochiral anhydrides in a membrane reactor.

7. Use according to one or more of the preceding claims, characterized in that the reaction is operated in repetitive batch mode and the catalyst is washed in the membrane reactor between the reactions.

8. Use according to claim 7, characterized in that the washing is carried out in such a way that no product molecule remains chemically or physically bound in the reactor.

9. Use according to one or more of the preceding claims, characterized in that the reaction is carried out under conditions which prevent a reaction of the anhydride with the catalyst.