EP1087927A1 - Method for the catalytic, asymmetric disubstitution of carboxylic acid amides with two different grignard reagents - Google Patents

Abstract

The invention relates to a method for asymmetrically disubstituting carboxylic acid amides on the geminal carbonyl-C-atom using two different grignard reagents in the presence of a metal alcoholate compound used as a catalyst and in the presence of another organometallic compound used as a co-catalyst.

Description

         The present invention relates to a process for the disubstitution of carboxylic acid amides with 2 different Grignard reagents in the presence of an organometallic compound as catalyst and another organometallic compound as cocatalyst. It is already known from the prior art, in particular from the publication in Jahresheften Chem. 93, pages 469 to 475 (1962), that the reaction of carboxamides, such as formamide, with two different Grignard reagents gives asymmetrical alkylated amines. The yield of these products is so low, up to 15% at most, that these reaction products can at most be described as by-products. The task therefore arose of producing asymmetrically substituted amino compounds not only as by-products in the reaction of carboxamides with 2 different Grignard reagents, but also in a usable yield and with a sufficient possibility of varying the substituents. By providing the process according to the invention, it is possible to prepare asymmetrically substituted amino compounds with a significantly improved yield. The subject matter of the present invention is therefore a process for preparing compounds of the general formula (I) ##STR1## R', R2 and R3 independently of one another H, A, Ar,-Si(R6) 3,-Sn(R6) 3,- SR', -OR', -NR8R9 or R' and R2 or R and R3 or R and R9 can be connected to one another and together form a cyclic ring with 3 to 8 carbon atoms which optionally has at least one further heteroatom in addition to nitrogen selected from the group -S-, -O- and -NR6-, R4 and R5 A Ar-Si(R6) 3, -Sn(R6) 3, -SR7, -oR7, -NR3R9 where R8 and R9 are the have the given meanings or R 8 and R 9 are connected to one another and together form a cyclic ring having 3 to 8 carbon atoms which, in addition to a nitrogen atom, optionally contains at least one heteroatom selected from the group -S-, -O- and -NR5- ; or where two R4 radicals are connected to one another and together form a cyclic ring with 3 to 8 carbon atoms which, in addition to a nitrogen atom, optionally also contains at least one heteroatom selected from the group -S-, -O- and -NR6-, with which Provided that R4 and R5 may each have a maximum of one hydrogen atom in the ss position. R6, R7, R8 and R9, independently of one another, are A or Ar, A is a straight-chain or branched alkyl radical having 1 to 10 carbon atoms, a straight-chain or branched alkenyl radical having 2 to 10 carbon atoms, or a straight-chain or branched alkyne radical having 2-10 carbon atoms or substituted or unsubstituted cycloalkyl radical having 3-8 carbon atoms, mono- or polyunsaturated cycloalkyl radical having 3-8 carbon atoms and Ar is a substituted or unsubstituted aryl radical having 6-20 carbon atoms, characterized in that a compound of the general formula (II) EMI3.1 in which Ri, R2 and R3 have the meanings given for formula (I), by reaction with one nucleophilic reagent of the general formula (IIIa) and one nucleophilic reagent of the general formula (IIIb) Z-R4 (IIIa ) Z-R5 (IIIb) wherein R4 and R5 has the meaning given for formula (I), and Z Li or MgX with X Hal and Hal Cl, Br, or I. According to the invention, the process in the presence of catalytic amounts of a metal alcoholate general formula (IV): MX4-n (OR) n (IV) where M is titanium, zirconium and hafnium, X is Cl, Br, I and R is alkyl having 1 to 10 carbon atoms or aryl having 6 to 20 carbon atoms n is an integer from 1 to 4. Metal alkoxides in which R is isopropyl are preferably used. Particular preference is given to using Ti(OiPr) 4 as the metal alkoxide, where iPr corresponds to an isopropyl radical. The invention also relates to a corresponding process which is carried out in the presence of a cocatalyst. The present invention therefore also includes a process which is carried out using metal isopropylates and alkylsilyl halides as cocatalysts; namely metal isopropylates of the general formula (V) and alkylsilyl halides of the general formula (VI) M'S+) (O-iPropyl) s (V) R3SiX (VI) or of the general formula (VIl) Ro-(X) m-Si-Y- (Si) p-(X) q-Ro (VII) wherein M'Al, Ca, Na, K, Si or Mg, preferably Mg or Na s is an integer from 1 to 4 and the oxidation state of the metal R is alkyl with 1 up to 10 carbon atoms or aryl with 6 to 20 carbon atoms X F, Cl, Br, CN m 0.1, n 1 to 10, o 0.2.3, p 0.1 and q 0.1, with provided that 0=3 and Yw (CH2) n when m=0. The subject matter of the invention is therefore also a process which is characterized in that a) a carboxamide of the general formula (II), 1-15 mol % of a metal alcoholate selected from the group consisting of titanium alcoholate, zirconium alcoholate and hafnium alcoholate, based on the carboxamide, and optionally a cocatalyst at room temperature under an inert gas atmosphere in a solvent selected from the group consisting of toluene, THF, n-hexane, benzene and diethyl ether, b) a solution containing two nucleophilic reagents of the general formula (IIIa) and (IIIb) is added dropwise and c) allows the reaction to continue with stirring and, after the reaction has ended, is worked up in the usual way. Experiments have shown that with two nucleophilic reagents of the general formulas (IIIa) and (IIIb), which can be Grignard reagents and are added to the reaction mixture as such, carboxamides of the general formula (II) can be converted in a simple manner in the presence of catalytic amounts of titanium alcoholate, zirconium alcoholate or hafnium alcoholate to form asymmetrically substituted compounds of the general formula (I). According to the invention, carboxylic acid amides of the general formula (II) in which R′, R2 and R3 independently of one another can assume the following meanings can be reacted with good yields by the process described here: H or A d. H. branched or unbranched alkyl having 1 to 10 carbon atoms, such as methyl, ethyl, n- or i-propyl, n-, sec- or t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and suitable isomers thereof, or cycloalkyl with 3-8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or corresponding methyl- or ethyl-substituted cycloalkyl groups or mono- or polyunsaturated cycloalkyl groups, such as cyclopentenyl or cyclopentadienyl or branched or unbranched alkenyl 2 to 10 carbon atoms, such as allyl, vinyl, isopropenyl, propenyl or branched or unbranched alkynyl having 2 to 10 carbon atoms, such as ethynyl, propynyl or aryl having 6 to 20 carbon atoms, optionally unsubstituted or mono- or polysubstituted, such as phenyl, naphthyl, anthryl, phenanthryl, substituted one or more times by substituents selected from the group consisting of NO 2 , F, Cl, Br, NH 2 , NHA, NA 2 , OH and OA, where A can have the meanings given above, single, multiple or fully halogenated, preferably fluorinated, or aralkenyl or aralkinyl, in which case the aryl, alkenyl and alkynyl group can assume the meanings given, such as e.g. B. in phenylethynyl. Good yields are also achieved in particular with carboxylic acid amides in which R1 and R2 or R1 and R3 together form a cyclic ring with 3-8 carbon atoms which, in addition to nitrogen, contains further heteroatoms such as -S-, -O- or -NR6- . Particular preference is given here to compounds in which R' and R2 or R' and R3 form a simple cyclic ring which includes the nitrogen of the carboxamide or in which R' and R2 or R' and R3 form a cyclic ring which includes a Oxygen atom contains as a further heteroatom. In this way, so high yields are achieved when compounds such. B. EMI7.1 can be used as starting materials. As a nucleophilic reagent, Grignard or lithium-organic compounds of the general formulas (IIIa) and (IIIb) can be used, in which the radicals R4 and R5 are preferably an alkyl radical having 1 to 10 carbon atoms, such as methyl, ethyl, n- or i-propyl, n-, sec- or t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and their suitable isomers, or cycloalkyl with 3-8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, Cyclohexyl, cycloheptyl, cyclooctyl or corresponding methyl- or ethyl-substituted cycloalkyl groups or mono- or polyunsaturated cycloalkyl groups, such as cyclopentenyl or cyclopentadienyl, or branched or unbranched alkenyl having 2 to 10 carbon atoms, such as allyl, vinyl, isopropenyl, propenyl or branched or unbranched alkynyl having 2 to 10 carbon atoms, such as ethynyl, propynyl, or for aryl radicals having 6 to 20 carbon atoms, optionally unsubstituted or mono- or polysubstituted, such as phenyl, naphthyl, anthryl, phenanthryl, mono- or polysubstituted by substituents , selected from the group NO2, F, Cl, Br, NH2, NHA, NA2, OH and OA, where A can have the meanings given above, can be mono-, poly- or fully halogenated, preferably fluorinated, or or for aralkyl radicals with 7 to 20 carbon atoms, such as benzyl, optionally substituted one or more times by substituents selected from the group consisting of NO2, F, Cl, Br, NH2, NHA, NA2, OH and OA, where A can have the meanings given above, simple , Poly or fully halogenated, preferably fluorinated, may be or for aralkenyl or. Aralkynyl radicals, in each case the aryl, alkenyl and alkynyl group can assume the meanings given, such as. B. in phenylethynyl. Furthermore, the radicals R4 and R5 in the general formula (IIIa) and (IIIb) can represent -Si(R6)3, -Sn(R5)3, -SR7, -oR7-NR8R9 where R6 is R', R8 and R9 independently of one another assume the meanings given above or R and R9 are connected to one another and together form a cyclic ring having 3 to 8 carbon atoms which, in addition to a nitrogen atom, may also contain at least one heteroatom selected from the group -S-, -O- and -NR6- can be included ; The radical Z in the general formulas (IIIa) and (IIIb) preferably represents a radical MgX where X is Cl or Br, or the radical Z is lithium. Grignard compounds such as: methylmagnesium bromide, ethylmagnesium bromide, n-propyl-magnesium bromide, i-, sec-butylmagnnesium bromide, n hexylmagnesium bromide, cyclohexylmagnesium chloride are particularly preferred. Esium bromide, cyclopentylmagnesium bromide, cyclopentylmagnesium chloride, phenylmagnesium bromide, benzylmagnesium chloride used for implementation . It was also found that the geminal asymmetrical dialkylation reactions according to the invention only start at room temperature when a cocatalyst is added and lead to complete conversion of the starting materials in a relatively short reaction time. Metal isopropylates and alkylsilyl halides are suitable as cocatalysts in this reaction. In particular, these are metal isopropylates of the general formula (V) and alkylsilyl halides of the general formula (VI) M' (0-iPropy!) s (V) R3SiX (VI) or of the general formula (VII) Ro-(X)m-Si- Y-(Si)p-(X)q-Ro(X)m-Si-Y-(Si)p-(X)q-Ro (VII) wherein M'Al, Ca, Na, K, Si or Mg , preferably Mg or Na s is an integer from 1 to 4 and the oxidation state of the metal R is alkyl having 1 to 10 carbon atoms or aryl having 6 to 20 carbon atoms X F, Cl, Br, CN m 0.1, n 1 to 10, o 0.2.3, p 0.1 and q 0.1, with the proviso that 0=3 and Yt (CH2) n when m=0. Preference is given to using metal isopropoxides in which s is an integer from 1 to 4 and the oxidation state of the metal and M' is Al, Ca, Na, K, Si or Mg. Particular preference is given to Mg or Na. Alkylsilyl halides in which R is alkyl having 1 to 6 carbon atoms are preferably used. Particular preference is given to those in which R is alkyl having 1 to 3 carbon atoms and X is chlorine. In particular, i.a. the following silicon compounds are suitable as co-catalysts: (CH3) 3SiCl (CH3) 2CISi (CH2) 2SiCl (CH3) 2 (CH3) 2CISi (CH2) 3CN [ (CH3) 3Si] 20 [ (CH3) 3Si] 2NH and [(CH3) 3Si] 2 It was found that the addition of 0.7 to 1.2 mol, in particular 0.9 to 1.1 mol, of a cocatalyst, based on one mole of starting material, leads to improved results, such as B. higher yields, lower reaction temperature or shorter reaction times. As can be shown with the aid of examples, complete conversion of the carboxylic acid amide according to the general reaction equation (Eq. 1) has already taken place after one hour under favorable conditions: 3 <tb> R\1R3R4 <SEP> R5 <SEP> cat. <SEP> Ti <SEP> (OiPr) <SEP> 4 <SEP> R <SEP> R <tb> <SEP> N- <SEP> +Mg <SEP> +Mg----N-R <SEP> (G ). <SEP> 1) <tb> '2 <SEP> XO <SEP> X'9 <SEP> X <SEP> Cocatalyst <SEP> R2 <SEP> Rs <tb> To carry out the process according to the invention, commercially available metal alcoholate can be selected from from the group of titanium alcoholate, zirconium alcoholate and hafnium alcoholate can be used as a catalyst. Titanium tetraisopropylate is preferably used. The metal alkoxide, preferably titanium tetraisopropylate, is used as a solution in a suitable, pre-dried solvent. Suitable solvents are e.g. B. aliphatic or aromatic hydrocarbons or ethers. Preference is given to using solvents selected from the group consisting of toluene, THF, n-hexane, benzene and diethyl ether, which are dried before the reaction by methods known to those skilled in the art. Drying can be accomplished using magnesium sulfate, calcium chloride, sodium, potassium hydroxide, or other methods. A preferred embodiment of the process according to the invention is that the titanium tetraisopropoxide used as catalyst is used in an amount of 1 to 15, preferably 1.5 to 14, in particular 2 to 10, and very particularly preferably 3 to 6 mol% based on one mole of amide used as starting material is initially introduced in the form of a solution which is adjusted to a temperature of 10 to 30 C, preferably to 15-25 C, particularly preferably to a temperature of about 20 C. Under an inert gas atmosphere (nitrogen or argon), the starting material is slowly added dropwise, either as such in liquid form or dissolved in a solvent selected from the group consisting of toluene, THF, n-hexane, benzene and diethyl ether, with stirring. The amount of cocatalyst to be reacted is then added dropwise, if necessary also in a solvent. The resulting reaction mixture is for a short time, i. H. stirred for a few minutes at a constant temperature. So much nucleophilic reagent of the general formula (IIIa) and (IIIb), in particular Grignard reagents, is then slowly added to the resulting reaction mixture that a substitution of the geminal carbonyl C atom by two different substituents, i. H. ie an asymmetric substitution of the geminal carbonyl carbon atom can take place. The nucleophilic reagents according to the invention, prepared by methods well known to those skilled in the art, should be added so slowly that the temperature of the reaction mixture does not exceed 50.degree. It is advantageous if the addition of the nucleophilic reagents, i. H. the Grignard reagents or the lithium compounds with thorough mixing, preferably with intensive stirring. In order to shift the reaction equilibrium towards the desired asymmetrically substituted product, the nucleophilic reagents used, preferably Grignard reagents, are each added in amounts of 0.7 to 1.2 mol per mol of reacting starting material. The Grignard reagents are preferably added in amounts of 0.9 to 1.1 mol, based on 1 mol of starting material. After the addition of the Grignard reagents is complete, the reaction mixture is stirred at a constant temperature for some time until the reaction is complete. If no cocatalyst is added to the reaction mixture, the reaction temperature can be adjusted to about 80° C., preferably to 60 to 70° C., in particular to 65° C., after the addition of the nucleophilic reagents is complete and thorough mixing has taken place. According to the synthesis according to the invention, unsymmetrically substituted amino compounds of the general formula (I) can thus be prepared with good or satisfactory yields within reasonable reaction times. Advantageously, by adding one of the catalysts in conjunction with one of the described cocatalyst compounds of the general formulas (V), (VI) or (VII), the reaction times can be reduced considerably, in the best case to one hour, without accepting a reduction in the yields achieved to have to. The use of a catalyst system consisting of a metal alkoxide selected from the group consisting of titanium alkoxide, zirconium alkoxide and hafnium alkoxide as a catalyst and a compound of the general formulas (V), (VI) or (VII) with the meanings given above is also the subject of the present invention . As is the use of this catalyst system in the preparation of the asymmetrically substituted compounds of the general formula (I). For example, 5 mmol of starting material are added dropwise at 20° C. under an inert gas atmosphere to a solution of 3 mol % of titanium tetraisopropylate in 40 ml of dried tetrahydrofuran, with stirring. 5 mmol of cocatalyst, also taken up in dried tetrahydrofuran, are slowly added to this mixture with stirring. The mixture is stirred at 20° C. for 5 minutes and then a solution of 6 mmol each of two different Grignard reagents is slowly added so that the temperature of the reaction mixture does not rise above 50° C. Stirring is continued for a further hour until the reaction is complete. After the reaction according to the invention, the reaction mixture can be worked up in a manner known to those skilled in the art. Here, the products as salts with the help of hydrochloric acid solutions z. B. a 1 molar ethereal hydrochloric acid solution, precipitated and filtered off, and, if necessary, purified by recrystallization. To remove the Lewis acid, a suitable amount of saturated ammonium chloride solution and water can be added, for example, and stirring can be continued intensively for several hours (1-3 hours). The resulting precipitate is separated off and washed with a little ether, preferably diethyl ether. The filtrate is made basic (pH>10) by adding a suitable base, such as a NaOH, KOH, sodium or potassium carbonate solution, preferably sodium hydroxide solution. The phases that form are then separated and the aqueous phase extracted several times (e.g. three times with 30 ml each time in the special case given above) with diethyl ether. The combined organic phases are washed with (e.g. 15 ml) saturated sodium chloride solution and can be dried over potassium carbonate, magnesium sulfate or sodium sulfate and filtered. The products can be purified in various ways by methods known to those skilled in the art, such as B. in the following manner: 1. They are precipitated as hydrochlorides with 1M ethereal hydrochloric acid solution and filtered off (the product obtained is purified by recrystallization, if necessary). 2. The organic phase is extracted several times with a 0.5 M acid solution, preferably an aqueous hydrochloric acid solution. The extract obtained is adjusted to pH>10 with the aid of bases, preferably 2M sodium hydroxide solution, and extracted at least once, preferably several times, with diethyl ether. The organic phases obtained in this way, which contain the reaction product, can optionally be dried over potassium carbonate, magnesium sulfate or sodium sulfate and freed from the organic solvent under reduced pressure. 3. Furthermore, it is possible to isolate the reaction product by the organic solvent center! removed in vacuo and the residue that remains is separated by column chromatography to isolate the reaction product. Instead of the general description of how to carry out the process given above, the Grignard reagents can also be replaced by the corresponding lithium compounds. Like the Grignard compounds, the corresponding lithium compounds can be prepared by methods generally known to those skilled in the art and can be reacted according to the invention in the same way as described above. The compounds of the general formula (I) prepared according to the invention can, for. B. as intermediates for the preparation of sulfur- or selenium-containing amines for the chiral catalysis of diethylzinc syntheses (literature: Werth, Thomas; Tetrahedron Lett. 36; 1995, 78497852, Werth, Thomas et all. Helv. Chim. Acta 79, 1996,1957-1966) can be used. In order to illustrate and to provide a better understanding of the present invention, the following examples are given. However, due to the general validity of the invention principle described, these are not suitable for extending the scope of protection of the examples Titanium tetraisopropylate-induced asymmetric dialkylation of carboxamides using 2 different Grignard reagents carried out : EMI16.1 <tb> R'R3, <SEP> R4, <SEP> RS <SEP> cat. <SEP> Ti <SEP> (OiPr) <SEP> 4 <SEP> Rs <SEP> R3 <SEP> 4 <tb> <SEP> (G1. <SEP> 1) <tb> RzO <SEP> X <SEP > X <SEP> cocatalyst <SEP> Rz <tb> <SEP> amide <SEP> product <SEP> from-R4MgX/reaction <tb> <SEP> yield <SEP> R5MgX <SEP> conditions <tb> <SEP> m <SEP> nMeMgBr <SEP> lh/25 C/ <tb> <SEP> /PhMgBr <SEP> 3mol% <tb> <SEP> Ti <SEP> (OiPr) <SEP> 4/5 <tb> <SEP > mmol <SEP> Cokat <tb> <SEP> PhMgBr/lh/RT/ <tb> <SEP> 81% <SEP> BnMgCl <SEP> 3mol% <tb> <SEP> N <SEP> (OiPr) <tb > <SEP> 0 <tb> <SEP> MeMgBr <SEP> 3mo1% <tb> <SEP> 0 <SEP> N <SEP> 79%/PhMgBr <SEP> Ti <SEP> (OiPr) <SEP> 4/ 5 <tb> <SEP> mmol <SEP> Cokat <tb> <SEP> U <tb> Me = methyl, Ph = phenyl, iPr = iso-propyl, Bn = benzyl, cokat = (CH3) 3SiC ! Table 1: Ti (OiPr) 4-induced conversion of carboxamides with R4MgX and R5MgX
    

Claims

PATENT CLAIMS 1. Process for preparing compounds of general formula (1) EMI17.1 wherein R', R2 and R3 are independent of each other H, A, Ar,-Si(R5)3,-Sn(R5)3,-SR7,-oR7,-NR8R9 or Rr and R2, respectively

R and R3 or R8 and R9 can be connected to one another and together form a cyclic ring having 3 to 8 carbon atoms which, in addition to nitrogen, optionally contains at least one further heteroatom selected from the group —S—,—O—and—NR5— , R4 and R5 A, Ar,-Si(R6)3,-Sn(R6)3,-SR7,-oR7,-NR8R9 where R8 and R9 have the meanings given or R8 and R9 are connected to one another and together form a cyclic ring having 3 to 8 carbon atoms which, in addition to a nitrogen atom, optionally contains at least one heteroatom selected from the group S-, -O- and -NR6- ;

or where two R4 radicals are connected to each other and together form a cyclic ring having 3 to 8 carbon atoms, which optionally in addition to a nitrogen atom also contains at least one heteroatom selected from the group -S-, -O- and -NR5-, with the proviso that R4 and R5 may each have a maximum of one hydrogen atom in the R position.

R6, R7, R8 and R9 independently of one another A or Ar, A is a straight-chain or branched alkyl radical with 1 to 10 C Atoms, straight-chain or branched alkenyl radical with 2 to 10 carbon atoms, or straight-chain or branched alkynyl radical with 2-10 carbon atoms or substituted or unsubstituted cycloalkyl radical with 3-8 carbon atoms, mono- or polyunsaturated cycloalkyl radical with 3-8 carbon atoms and Ar is a substituted or unsubstituted aryl radical with 6-20 C Atoms mean, characterized in that a compound of general formula (II) EMI18.1 in which R, R2 and R3 have the meanings given above for formula (I),

by reaction with in each case a reagent of the general formula (IIIa) and a nucleophilic reagent of the general formula (IIIb) Z-R4 (IIIa) Z-R5 (IIIb) in which R4 and R5 have the meaning given for formula (I), and Z Li or MgX with X Hal and Hal Cl, Br, or I mean 2. The method according to claim 1, characterized in that it is in Presence of catalytic amounts of a metal alkoxide selected from the group consisting of titanium alkoxide, zirconium alkoxide and hafnium alcoholate, is carried out.

3. Process according to claims 1 to 2, characterized in that it is carried out in the presence of a cocatalyst.

4. Process according to Claims 1 to 3, characterized in that it is carried out in the presence of a metal isopropylate or an alkylsilyl halide as cocatalyst.

5. Process according to Claims 1 to 4, characterized in that a metal isopropylate of the general formula (V) or an alkylsilyl halide of the general formula (VI) is used as the cocatalyst M' (0-iPropy !) s (V) R3SiX (VI) or the general formula (Vll) R0-(X)m-Si-Y-(Si)p-(X)q-R0 (VII) wherein M'Al, Ca, Na, K, Si or Mg, preferably Mg or Na s an integer from 1 to 4 and the oxidation state of the metal R alkyl with 1 to 10 carbon atoms or aryl with 6 to 20 carbon atoms X F, Cl, Br, CN m 0.1, n 1 to 10, o 0.2.3, p 0.1 and q 0, 1 mean, with the proviso that

that 0=3 and Yw (CH2) n when m=0 is used.

6. The method according to one or more of the preceding claims, characterized in that a metal alkoxide of the general formula (IV) MX4-n (OR) n (IV) wherein M is titanium, zirconium and hafnium, X is Cl, Br, I and R is alkyl having 1 to 10 carbon atoms or aryl having 6 to 20 carbon atoms n is an integer from 1 to 4, is used as the catalyst.

7. Process according to the preceding claims, characterized in that a) a carboxylic acid amide of the general formula (II), 1-15 mol % of a metal alcoholate selected from the group consisting of titanium alcoholate, zirconium alcoholate and hafnium alcoholate, based on the Carboxamide, and optionally the cocatalyst at 10 30 C under an inert gas atmosphere in a solvent selected from the group of toluene, THF, n-hexane, benzene and diethyl ether, b) a solution containing two different nucleophiles Reagents of general formulas (IIIa)

and (IIIb), wherein R4 and R5 have the meanings given in claim 1 and Xhas the meanings given in the preceding claims, is added dropwise and c) after-reacts with stirring! eats and after finishing the Reaction worked up in a customary manner. 8. Process according to Claim 7, characterized in that process step a) is carried out at a temperature of 15 to 25 C.

9. Process according to Claim 7, characterized in that process step a) is carried out at room temperature.

10. The method according to one or more of the preceding claims, characterized in that as nucleophilic reagents Lithium compounds of the general formulas (IIIa) and (IIIb) are used, in which R4 and R5 can have the meanings given in claim 1 or claim 7.

11. The method according to one or more of the preceding claims, characterized in that the nucleophilic reagents of the general formulas (IIIa) and (IIIb) are used in which R4 and R5 are methyl, ethyl, n- or i-propyl, i-, sec- or tert-butyl, n hexyl, cyclopentyl, cyclohexyl, allyl, vinyl, phenyl or benzyl.

12. Process according to one or more of the preceding Claims, characterized in that a compound according to the general formula (II) is reacted, in which RÚ, Rê and R independently of one another are H, methyl, ethyl, n- or i-propyl, i-, sec- or tert-butyl, n-hexyl, phenyl or benzyl.

13. Catalyst system consisting of a metal alkoxide of the general formula (IV) MX4-n(OR)n (IV) where M is titanium, zirconium and hafnium, X is Cl, Br, I and R is alkyl having 1 to 10 carbon atoms or aryl having 6 to 20 carbon atoms and a cocatalyst of the general formula (V), (VI) M' (0-iPropy !) s (V) R3SiX (VI) or the general formula (VII) R0-(X)m-Si-Y-(Si)p-(X)q-R0(X)m-Si-Y-(Si)p-(X) q-R0 (VII) wherein M'Al, Ca, Na, K, Si or Mg, preferably Mg or Na s is an integer from 1 to 4 and the oxidation state of metal R alkyl with 1 to 10 carbon atoms or aryl with 6 to 20 carbon atoms X F,

Cl, Br, CN m 0.1, n 1 to 10, o 0.2.3, p 0.1 and q 0.1 with the proviso that 0=3 and Y#(CH2)n when m=0, is used.

14. Catalyst system according to claim 13, containing a compound selected from the group Na (OiPr) Mg (OiPr) 2 Al(OiPr)3(CH3)3SiCl(CH3)2CISi(CH2)2SiC)(CH3)2(CH3)2CISi(CH2)3CN[(CH3)3Si]20[(CH3)3Si]2NH and [(CH3)3Si ] 2 as a cocatalyst.

15. Catalyst system according to claim 13 containing titanium tetraisopropylate as the metal alkoxide.

16. Use of a catalyst system according to claims 13 to 15 in a method according to one or more of claims 1 to 12.