EP1341828A1 - Optically active polymer with epoxide functions, method for preparing same, and use thereof - Google Patents

Abstract

The invention concerns an optically active polymer obtainable by free radical or anionic polymerisation of an optically active ethylene monomer with epoxide function bearing at least a chiral centre with a copolymerisable ethylene monomer. An example of such a polymer is an optically active copolymer consisting of two types of repeat units A and B of formula: (A), (B), wherein R<0> to R<12>, X, Y<1> and Y<2>, B, * and n are such as defined in Claim 1. Another example is an optically active monomer consisting of two types of repeat units A and C, A being as defined above and C corresponding to formula (C). Said polymers are useful, optionally after the epoxide functions are opened, for immobilising enzymes, as polymeric matrix for chiral chromatography, as polymeric support for solid phase synthesis, as ligand for preparing transition metal complexes in regioselective catalysis or as chiral inducer in regioselective catalyst.

Description

 OPTICALLY ACTIVE POLYMER WITH EPOXIDE FUNCTIONS,

PROCESS FOR PREPARING SAID POLYMER, AND USE THEREOF

The invention relates to an optically active polymer having reactive epoxy functions, each epoxy function carrying at least one chiral center. The invention furthermore relates to a process for the preparation of said polymer, in particular by radical route.

The invention also covers an optically active polymer derived from the previous one by opening the epoxy functions (designated polymer modified below) as well as its preparation process.

According to another of its aspects, the invention relates to the use of this polymer as a polymer matrix in chemical chromatography, as a polymer support in asymmetric synthesis on a solid phase or as a ligand in the preparation of transition metal complexes intended for asymmetric catalysis. , as well as the use of said polymer as reactive polymeric material for the immobilization of enzymes.

In addition, the invention provides methods for preparing said polymers which allow modulation of physical properties such as appearance, porosity, specific surface, size of the beads and resistance. The main advantages of the polymer of the invention are its optically active nature and its reactivity. The chirality is notably carried by the epoxy functions. Reactivity is linked to the presence of epoxide functions within the polymer backbone. These properties of the polymer of the invention make it particularly suitable for use in chiral chromatography, after opening of the reactive epoxy functions.

Preparative or analytical chiral chromatography is experiencing considerable growth due to the increasingly severe constraints linked to regulations on drugs and food additives which oblige manufacturers to offer pure enantiomers. Chiral chromatography is particularly advantageous insofar as it allows the resolution of racemic mixtures in the case of molecules of low molecular mass. The stationary chiral phases industrially developed and known to date are in particular those described in Synlett, 1998, 4, 344-360 which are based on polysaccharides; those described in Angew. Chem. Int. Ed. 1998, 37, 1020-1043 which are cellulose triacetates, cellulose benzoates, cellulose and amylose phenylcarbamates or cellulose aralkylcarbamates; as well as those described in High Resolution Chromatogr. 1998, 21, 267-281, which are silicas modified with bovine or human serum albumin, chiral phases of Pirkle or cyclodextrin type or chiral phases modified with crown ethers. The opening of the chiral epoxide functions of the polymer of the invention with a view to its use in chiral chromatography is carried out according to the invention by the action of a nucleophilic agent, optionally chiral, under conditions suitable for causing the opening of the epoxy functions . This opening reaction allows, if necessary, a functionalization of said polymer. Examples of usable nucleophilic agents are phosphines, amines, guanidines, thiols and thiolates, ammonia, alcohols and alcoholates, water, selenols and their salts, sulfites and bisulfites and carbanions.

After opening of the epoxy functions, the polymer of the invention is not only usable in chiral chromatography but also as a support in asymmetric synthesis on solid phase or as a chiral ligand capable of coordinating with a transition metal for the preparation of metal complexes usable in asymmetric catalysis.

More specifically, the invention relates to an optically active polymer which can be obtained by radical or anionic polymerization of an optically active ethylenic monomer with an epoxide function carrying at least one chiral center optionally in the presence of one or more other copolymerizable ethylenic monomers.

By optically active polymer is meant a polymer having an enantiomeric excess of at least 70%, preferably at least 75%, for example at least 80% and more preferably at least 90%, such as d '' at least 95%. The copolymerizable ethylenic monomer can comprise one or more ethylenic double bonds. When it comprises more than one ethylenic double bond, it is preferable that these be conjugated to each other. In general, the copolymerizable ethylene monomers include olefinic hydrocarbons such as styrene, α-methylstyrene, divinylbenzene, vinyltoluene, vinylfuran, vinylthiophene, vinylpyrrole and styrenesulfonic acids but also dienes of the isoprene and butadiene type; halogenated monomers of the vinyl chloride, chloroprene, vinylidene chloride, vinylidene fluoride and vinyl fluoride type; unsaturated acids of the acrylic acid, methacrylic acid and crotonic acid type; unsaturated esters of the vinyl acetate, methyl methacrylate, ethyl acrylate, methyl acrylate and 2-hydroxyethyl acrylate or methacrylate type; unsaturated amides such as acrylamide, N, N-dimethylacrylamide, methylenebisacrylamide and N-vinylpyrrolidone; unsaturated nitriles of the acrylonitrile type; unsaturated ethers such as vinyl ether; vinylpyridines, diethyl vinylphosphonate and sodium styrenesulfonate.

The preferred polymers of the invention are copolymers resulting from the polymerization of an ethylenic monomer which can be polymerized with an optically active ethylenic monomer with an epoxy function carrying at least one chiral center.

In general, the molar ratio of the fraction derived from the epoxy-functional optically active ethylenic monomer to the fraction derived from the copolymerizable ethylenic monomer in the polymer of the invention varies from 1-100: 0-99, for example from 10- 100: 0-90, preferably 30-100: 0-70, preferred ratios being 100: 0, 50:50 and 30:70.

According to a first preferred embodiment of the invention, each ethylenic monomer comprises, at the alpha of the ethylenic double bond, a carbonyl, nitrile, ester, amide or ether function, and this in order to increase its reactivity. More preferably, it is an ester function which activates the ethylenic double bond.

Thus, a first preferred group of polymers of the invention consists of polymers in which: the copolymerizable ethylenic monomers, when they are present, comprise a carbonyl, ester, amide or ether function in alpha of the ethylenic double bond, and / or

the optically active ethylenic monomer with an epoxy function carrying at least one chiral center comprises a carbonyl, ester or amide function in alpha of the ethylenic double bond.

Among these polymers, those in which the epoxy-functional optically active ethylenic monomer has the formula I are preferred:

in which :

- * indicates the location of a carbon of stereochemistry R or S well determined, it being understood that when R ³ represents a hydrogen atom the carbon carrying R ³ is not chiral;

- n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4; - X represents -O-, -S- or -NT- where T represents a hydrogen atom; an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independently chosen from a hydrogen atom; or an alkyl, cycloalkyl or aryl group, said group being optionally substituted; it being understood that R ⁵ and R ⁶ may also represent 1-alkenyl.

According to a preferred variant, X represents O in formula I above. Advantageously, in formula I, R ° and R ³ independently represent a hydrogen atom, an optionally substituted aryl group, or an optionally substituted alkyl group, R ⁴ represents an optionally substituted alkyl group or an optionally substituted aryl group, and R ¹ and R ² independently represent a hydrogen atom or an optionally substituted alkyl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group.

Better still, in formula I, R °, R ¹ , R ² , R ³ , R ⁵ and R ⁶ represent a hydrogen atom; and R ⁴ represents an optionally substituted alkyl group, for example methyl.

As preferred copolymer of the epoxide of formula I above, the copolymers obtained by polymerization of said epoxide with a monomer of (meth) acrylate type are preferred.

By (meth) acrylate type monomer is understood in the context of the invention, an optionally substituted acrylate or methacrylate type monomer.

Preferred examples of (meth) acrylate monomers are the monomers of formula:

wherein R ⁷ , R ⁸ and R ⁹ independently represent a hydrogen atom; an optionally substituted alkyl group; an optionally substituted aryl group; an optionally substituted cycloalkyl group; or a polysiloxyl group; and P represents an optionally substituted alkyl group, an optionally substituted aryl group or an optionally substituted cycloalkyl group, or OP represents a polysiloxyl group.

The term “polysiloxyl group” is understood to mean, according to the invention, a polyorganosiloxane chain attached by an oxygen atom to the skeleton of the compound of formula XI and in particular having at least two different units chosen from those of formula J ₃ SiOι _{/ 2} (unit M), J ₂ SiO (D unit), JSiO _3/2 (T unit) and SiO _4/2 (Q unit).

The radicals J are optionally substituted aliphatic or aromatic hydrocarbon radicals of alkyl type, linear or branched, d- C- ₁₈ , or (C ₆ -Ci8) aryl, it being understood that one or more of the radicals J in said chain polyorganosiloxane can also represent a hydrogen atom or a hydroxyl group. As the preferred type of polyorganosiloxane chains, those derived from polyorganosiloxane of formula XII are preferred:

in which: m is an integer greater than or equal to 2, preferably greater than or equal to

10 and J ¹ and J ² are as defined above for J, it being understood that J ¹ and / or J ² may also represent a hydrogen atom or a hydroxyl group.

More particularly, in formula XII above, it is preferred that J ¹ and or J ² represent (Cι-C ₆ ) alkyl, advantageously methyl. Another preferred subgroup of polymers of the invention consists of copolymers obtainable by polymerization of an optically active monomer having epoxide functions with a copolymerizable ethylenic monomer comprising two ethylenic double bonds each having a carbonyl, ester or amide group. double bond alpha. Among this other group of polymers, there are more particularly those consisting of the following two types of recurring units A and B, of formula:

the motif A carrying at least one optically active chiral center at the epoxide function; in which: - * indicates the location of a carbon of stereochemistry R or S well determined, it being understood that when R ³ represents a hydrogen atom the carbon carrying R ³ is not chiral;

- n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4;

- X, Y ¹ and Y ² are independently chosen from -O-, -S- and -NT- where T represents a hydrogen atom, an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- B represents a divalent radical chosen from alkylene; cycloalkylene; alkylene interrupted by one or more arylene and / or cycloalkylene groups; or arylene; each of the alkylene, cycloalkylene or arylene groups being optionally substituted;

- R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are independently chosen from a hydrogen atom, a alkyl, cycloalkyl or aryl group, said group being optionally substituted;

R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , and R ¹² independently represent optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkylcarbonyloxy or optionally substituted arylcarbonyloxy; it being understood that R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ¹¹ and R ¹² can also represent 1-alkenyl, and that R ⁷ , R ⁸ and R ⁹ can also represent a polysiloxyl group. In the context of the invention, 1-alkenyl is understood to mean an aliphatic hydrocarbon group comprising at least one double bond in position 1 and optionally one or more other double bonds conjugated to the first. Preferably, 1-alkenyl is in CICI _O -

In the context of the invention, the term “alkyl” means a saturated linear or branched hydrocarbon radical such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl, 1-ethylpropyl , hexyl, isohexyl, neohexyl, 1-methylpentyl, 3-methylpentyl, 1, 1-dimethylbutyl, 1, 3-dimethylbutyl, 2-ethylbutyl, 1-methyl-1-ethylpropyl.

Preferably, the alkyl radical comprises 1 to 10 carbon atoms, better still 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms.

By aryl is meant a monocyclic or polycyclic aromatic hydrocarbon radical. When said aryl radical is polycyclic, each of the monocyclic rings constituting it is an aromatic hydrocarbon radical. In this case, said monocyclic nuclei are either attached to each other by simple carbon-carbon bonds, either orthocondensed or pericondensed.

Advantageously, the aryl radicals have from 6 to 18 carbon atoms, better still from 6 to 10 carbon atoms. Examples of aryl groups include phenyl, naphthyl, anthryl or phenanthryl.

By cycloalkyl is meant, according to the invention, saturated, monocyclic or polycyclic hydrocarbon radicals. When the cycloalkyl group is polycyclic, it consists of several saturated hydrocarbon monocyclic rings, attached to each other by simple carbon-carbon bonds or / and of monocyclic rings having two by two at least two carbon atoms in common.

Advantageously, the cycloalkyl group is C ₃ -Cn such as cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl and norbornyl.

The expression "alkylene interrupted by one or more arylene and or cycloalkylene groups" means that B can represent any one of the following sequences: • -alk -T ° -alk ² -;

• -alk ¹ -T ° -; or

• -T ° -alk ¹ -; where T ° represents arylene or cycloalkylene, and, alk \ alk ² independently represent alkylene of identical or different size.

The substituents of the alkyl, cycloalkyl, aryl, cycloalkylene, alkylene or arylene radicals are any provided that they are inert under the radical polymerization conditions used for the preparation of said polymer. Thus, the substituents in question have no function capable of reacting with the constituents of the reaction medium, or capable of preventing the radical reactions involved in the preparation of the polymer of the invention.

Examples of substituents to be banned are bromine and iodine atoms, and nitro groups when these atoms and groups are carried by sp ³ carbons.

Similarly, the substituents derived from the compounds which can be used as free radical scavengers are to be avoided: examples are the substituents derived from hydroquinone, monotertiobutylhydroquinone, 2,5-ditertiobutylhydroquinone, paratertiobutylcatechol, parabenzoquinone or ditertiobutylparacresol.

As examples of suitable substituents, mention may be made of chlorine and fluorine atoms; alkyl radicals; perfluoroalkyl (and for example trifluoromethyl); aryl; perfluoroaryl; cycloalkyl; perfluorocycloalkyl; alkoxy; aryloxy; cycloalkyloxy; oxo; cyano; amino disubstituted by alkyl, aryl and / or cycloalkyl; -CONR ^a R ^b in which R ^a and R are independently chosen from H, alkyl, aryl and cycloalkyl, it being understood that R ^a and R ^b do not both represent a hydrogen atom; and -COOR ^c where R ^c is as defined above for R ^a . Other acceptable substituents are hydroxy groups and polyoxyalkylenated chains of the type of polyoxyethylenated chains having a degree of polymerization from 2 to 20. The bromine atoms can also be chosen as substituents provided that they are carried by sp carbon atoms ² . When T or one of R ° to R ¹² represents substituted alkyl, this can represent linear C ₁ -C ₁₀ alkyl (preferably linear C ₁ -C ₅ alkyl, for example methyl) substituted in position ω by a radical chosen from perfluoroalkyl (in particular (C-ι-Cιo) perfluoroalkyle); perfluoroaryl (especially (C ₆ -Ci ₈ ) pβrfluoroaryl); perfluorocycloalkyle (in particular C ₃ -

Cιι) perfluorocycloalkyle); and a polyoxyalkylene chain such as a polyoxyethylene chain.

When B represents substituted alkylene, this can represent linear C ₁ -C ₁₀ alkylene substituted by one or more fluorine atoms and, for example, perfluorinated alkylene.

Preferred meanings of X, Y ¹ and Y ² are an oxygen atom.

Preferably, B represents optionally substituted alkylene, preferably ethylene.

In unit A, R ° and R ³ independently represent preferably a hydrogen atom, an optionally substituted aryl group or an optionally substituted alkyl group; R ⁴ preferably represents optionally substituted alkyl or an optionally substituted aryl group; and R ¹ and R ² are preferably independently chosen from a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group; and R ⁵ and R ⁶ are preferably independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group.

In motif B, it is preferred that R ⁹ and R ¹⁰ are independently chosen from optionally substituted alkyl and an optionally substituted aryl group and that R ⁷ , R ⁸ , R ¹¹ and R ¹² independently represent a hydrogen atom, an alkyl group optionally substituted or an optionally substituted aryl group.

Among the preferred polymers above consisting of units A and B, it is preferred that R °, R ¹ , R ² , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ¹¹ and R ¹² represent a hydrogen atom; and R ⁴ , R ⁹ and R ¹⁰ represent a methyl group; and R ³ represents H, methyl or phenyl.

According to another preferred embodiment of the invention, the optically active polymer is prepared from an ethylenic monomer having a function epoxide comprising a carbonyl, ester, amide or ether function in alpha of the ethylenic double bond and of a copolymerizable monomer comprising at least two ethylenic double bonds. Preferably, each ethylenic double bond of the copolymerizable monomer is grafted to an alkylene or arylene group.

Among these polymers, there is a second preferred group of polymers of the invention, which consists of polymers composed of the following two recurring units A and C of formulas:

the motif A carrying at least one optically active chiral center at the epoxide function; in which :

- * indicates the possible location of a carbon of stereochemistry R or S well determined, it being understood that when R ³ represents a hydrogen atom, the carbon carrying R ³ is not chiral;

- n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4; - X is chosen from -O-, -S- and -NT- where T represents a hydrogen atom, an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- E is chosen from alkylene optionally substituted and optionally interrupted by one or more divalent groups - Si (A) (B) - where A and B are independently chosen from optionally substituted alkyl or aryl optionally substituted; the divalent group of formula -Ch ¹ -Ar ° -Ch ² - where Ch \ Ch ² independently represent a bond, an oxygen atom, a sulfur atom or -NT-, T being as defined above, and , Ar ° represents optionally substituted arylene; a relationship ; an oxygen atom; the divalent group -NT- in which T represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group; or a chain -Ar ¹ -X ¹ -alk-X ² -Ar ² - where Ar ¹ and Ar ² are independently chosen from optionally substituted arylene, alk represents optionally substituted alkylene and X ¹ , X ² independently represent O or -NT ° -, T ° being as defined above for T;

- R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are independently chosen from a hydrogen atom, a alkyl, cycloalkyl or aryl group, said group being optionally substituted;

R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , and R ¹⁸ , may also represent optionally substituted alkoxy; optionally substituted aryloxy; optionally substituted alkylcarbonyloxy; optionally substituted arylcarbonyloxy; or a polysiloxyl group; it being understood that R ⁵ , R ⁶ , R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ may also represent 1 - alkenyl, and R ¹³ , R ¹⁴ and R ¹⁵ may also represent a polysiloxyl group. The substituents of the alkyl, cycloalkyl, aryl, alkylene and arylene groups are as defined above.

Likewise, the alkyl, cycloalkyl, aryl, alkylene and arylene radicals are as defined above. Polysiloxyl is also as defined above. Preferably: - when E represents optionally substituted alkylene, it represents - (CH ₂ ) _n '- where n' is an integer between 1 and 10, such as 1, 2, 3, 4 or 5;

- When E represents optionally substituted arylene, it represents optionally substituted phenylene;

- when E represents alkylene interrupted by -Si (A) (B) -, it represents the group (CH ₂ ) ni -Si (A) (B) - (CH2) n2- where ni and n ₂ are independently an integer of 0 to 10, preferably 0, 1, 2, 3, 4 or 5 and A, B are as defined above;

- when E represents -Ar ¹ -X ¹ -alk-X ² -Ar ² -, it represents the group:

where n ¹ is as defined above; more particularly in this radical it is preferred that the phenyl groups are distributed in the para position.

It should be understood that the terms alkyl, cycloalkyl, aryl, arylene, alkenyl and polysiloxyl are as defined above for the recurring units A and B.

Among this preferred group of compounds, more particularly preferred are those which meet one or more of the following conditions i) to iii):

- i) X represents an oxygen atom;

- ii) R ° and R ³ independently represent a hydrogen atom; an optionally substituted aryl group; an optionally substituted alkyl group;

R ⁴ represents optionally substituted alkyl or an optionally substituted aryl group; and R ¹ and R ² are independently chosen from a hydrogen atom, an optionally substituted alkyl group; or an optionally substituted aryl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group. - iii) R °, R ¹ , R ² , R ⁵ , R ⁶ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ represents a hydrogen atom; E represents phenylene; n is 1; X represents an oxygen atom; R ⁴ represents methyl; and R ³ represents a hydrogen atom or a phenyl group.

The invention further relates to a process for preparing the optically active polymer of the invention. This process comprises the radical or anionic polymerization of an optically active monomer with an epoxy function carrying at least one chiral center, where appropriate in the presence of one or more other copolymerizable ethylenic monomers, this polymerization being carried out in the presence of 'a radical or anionic initiator. When the polymerization of the monomers is carried out by the radical route, the polymerization is initiated by thermoactivation of an appropriate initiator, preferably of the azo or peroxide type.

As an azo type initiator, mention may be made of 1, 1'-azobis (isobutyronitrile) or azobisisobutyronitrile (AIBN); 1, 1'-azobis (secpentylnitrile); 1, 1'-azobis (cyclohexanecarbonitrile); or phenylazotriphenylmethane.

Other radical polymerization initiators which can be used in the context of the invention are benzopinacole (1, 1, 2,2-tetraphenyl-1, 2-ethanediol), 1, 1, 2,2-tetraphenyl-1, 2 -dicyanoethane, 1, 1, 2,2-tetraphenyl-1,2-diphenoxyethane and 1, 1, 2,2-tetraphenyl-1, 2-bis (trimethylsilyloxy) ethane.

More particularly advantageously, the initiator is the AIBN.

Examples of initiators of the peroxide type include benzoyl peroxide, tert-butyl peroxide, sec-butyl peroxide, n-butyl peroxide, acetylene peroxide, lauryl peroxide, vinyl peroxide, tert-butyl peracetate, tert-butyl hydroperoxide, cumene hydroperoxide, 2,4-dichlorobenzoyl peroxide, tert-butyl perbenzoate, 1, 1-bis peroxide ( tert-butyl) -3,3,5-trimethylcyclohexane. The use of benzoyl peroxide is in particular illustrated in M. TANG, Process Biochemistry, vol. 34, 1999, 857.

As a variant, any of the following initiators can be used:

OOH

I CH ₂ -C (R ₂ ) OEt

C ₁₆ H ₃₃ (OCH ₂ CH ₂ ) ₂₀ - O-CO-CH-CH-COOH

CIVCOR-,

CH ₂ = C (CH ₃ ) -COOCH (CH ₃ ) -O-OtBu

Ci ₆ H ₃₃ (OCH ₂ CH ₂ ) ₂₀ -O-CO-CH ₂ -CH ₂ -C (O) OOtBu

EtOCO-CH-CH (COOH) - CH ₂ -C (R ₂ ) -OOH CH ₂ OEt

HORN., where Ri and R ₂ are chosen from H and CH ₃ .

Among these peroxides, benzoyl peroxide is preferred.

The radical polymerization reaction is carried out at a temperature sufficient to initiate the radical polymerization or at a higher temperature. This temperature depends in particular on the type of initiator used. Generally, a temperature between 50 and 150 ° C, better still between 60 and 110 ° C, in particular between 50 and 100 ° C, for example between 70 and 90 ° C. Alternatively, the polymerization is carried out anionically in the presence a stabilizer for the active center of the polymerization chosen from alkali metal tert-alcoholates; alkali metal halides; alkyd polydentate alcoholates; and aluminum alkyls.

The alkali metal tert-alcoholates are the alcoholates derived from the corresponding aliphatic alcohols in which the hydroxy function is attached to a tertiary alkyl radical: examples are lithium tert-butoxide; sodium tert-butoxide; potassium tert-butoxide; and 3-methyl-

Lithium 3-pentylate.

As a particularly suitable alkali metal halide, lithium chloride may be mentioned.

Polydentate alkali metal alcoholates are alcoholates having one or more electronegative atoms chosen from O, S and N, and more particularly chosen from O and N.

Examples are in particular lithium 2- (2-methoxyethoxy) ethylate; or any of the compounds of formula:

• CH ₃ O- (CH ₂ -CH ₂ -O) ₂ -Li;

• CH ₃ O-CH ₂ -CH ₂ -OR;

• CH ₃ O- (CH ₂ -CH (CH ₃ ) O) ₂ -Li;

• (CH ₃ ) ₂ N- (CH ₂ -CH ₂ -O) ₂ -Li; or • (CH ₃ ) ₂ N-CH ₂ -CH ₂ -O-Li.

The aluminum alkyls of formula AIE ¹ E ² E ³ in which E ¹ , E ² and E ³ independently represent alkyl, optionally substituted by alkoxy; or aryl optionally substituted with alkyl or alkoxy; alkoxy optionally substituted with alkyl; or aryloxy optionally substituted by alkyl or alkoxy.

The alkyl, alkoxy or aryl radicals are as defined above.

Examples of alkyl aluminum are in particular triethyl aluminum, and the compounds of formula:

in which E ⁴ represents H or CH ₃ .

Preferably, the stabilizer is chosen from lithium chloride; lithium tert-butoxide; and lithium 3-methyl-3-pentylate, the more particularly preferred stabilizer being lithium chloride. According to a preferred embodiment, the anionic polymerization is carried out by additionally incorporating into the reaction medium a polymerization initiator chosen from alkyllithium; alkali metal ester enolates; and primary and secondary alkali metal alcoholates.

Alkyl lithium denotes saturated or unsaturated aliphatic hydrocarbons in which one or more of the hydrogen atoms are replaced by lithium atoms. By aliphatic hydrocarbon is meant more particularly a saturated aliphatic hydrocarbon with a straight or branched chain optionally substituted by one or more radicals chosen from alkoxy or aryl itself optionally substituted by alkyl or alkoxy. Examples of such alkyllithium are the monolithium alkyllithium chosen from n-butyllithium, tert-butyllithium, 1, 1-diphenylhexyllithium, diphenylmethyllithium, 1, 1-diphenyl-3-methylpentyllithium and β-lithio- - methylstyrene.

Other examples of alkyllithium are dilithiated alkyllithium such as 1, 1, 4,4-tetraphenyl-1, 4-dilithiobutane or 1, 3-bis (2-lithio-2-isopropyl) benzene.

The alkali metal ester enolates are ester enolates derived from alkylcarboxylic acids and lower alkanols. Said alkylcarboxylic acids have a linear or branched alkyl radical as defined above carrying one or more carboxy groups: this alkyl radical is also optionally substituted by one or more aryl radicals themselves optionally substituted by alkyl or alkoxy. Said lower alkanols correspond to the formula G-OH where G represents a linear or branched alkyl group as defined above and is optionally substituted by one or more aryl radicals themselves optionally substituted by alkyl or alkoxy.

Examples of enolates of alkali metal esters are tert-butyl 2-lithioisobutyrate, methyl 2-lithioisobutyrate or its sodium equivalent, ethyl 2-lithioisobutyrate or its potassium equivalent, 2-lithio-2 , Dimethyl 2,4-trimethylglutarate, ditertbutyl 2-lithio-2,2,4-trimethyl-glutarate; isopropyl 2-lithio-isobutyrate and tert-butyl 2-sodio-propionate.

The primary and secondary alkali metal alcoholates are the alcoholates derived from the corresponding aliphatic alcohols in which the hydroxy function is attached to a secondary or primary alkyl radical. Preferred examples are lithium methylate, lithium ethylate and lithium propylate.

In a particularly advantageous manner, the initiator is chosen from sec-butyl lithium, diphenylmethyllithium and 1, 1, 4,4-tetraphenyl-1, 4-dilithiobutane.

According to a first preferred embodiment of the invention, a monomer of formula I as defined above is polymerized:

where R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , * and n are as defined above. Advantageously, said monomer of formula I is copolymerized with a monomer of formula XI:

in which R ⁷ , R ⁸ , R ⁹ and P are as defined above. Even more preferably, the process of the invention comprises the reaction of an optically active monomer with an epoxide function of formula I, in which:

- * indicates the location of a carbon of stereochemistry R or S well determined, it being understood that when R ³ represents a hydrogen atom the carbon carrying R ³ is not chiral;

- n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4;

- X represents -O-, -S- or -NT- where T represents a hydrogen atom; an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independently chosen from a hydrogen atom; an alkyl, cycloalkyl or aryl group, said group being optionally substituted; it being understood that R ⁵ and R ⁶ may also represent 1-alkenyl; with a copolymerizable monomer of formula II:

in which :

- Y ¹ , Y ² represents -O-, -S- or -NT- where T represents a hydrogen atom, an alkyl, cycloalkyl or aryl group, said group being optionally substituted; - B represents alkylene, cycloalkylene, arylene or alkylene interrupted by one or more arylene and / or cycloalkylene; each alkylene, cycloalkylene or arylene being optionally substituted;

- R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are independently chosen from a hydrogen atom, an alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyloxy or arylcarbonyloxy group, said group being optionally substituted; it being understood that R ⁷ , R ⁸ , R ¹¹ and R ¹² can also represent 1-alkenyl, and R ⁷ , R ⁸ and R ⁹ can also represent a polysiloxyl group.

In formulas I and II, 1-alkenyl is as defined above for the copolymer.

According to a preferred embodiment, X represents O; Y ¹ , Y ² both represent an oxygen atom and B represents an optionally substituted alkylene, or an optionally substituted arylene group.

Advantageously, in formula I, R ° and R ³ represent a hydrogen atom, an optionally substituted aryl group, an optionally substituted alkyl group, R ⁴ represents optionally substituted alkyl or an optionally substituted aryl group, and R ¹ and R ² independently represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group.

Furthermore, in formula II, it is preferred that R ⁹ and R ¹⁰ are independently chosen from optionally substituted alkyl and an optionally substituted aryl group and R ⁷ , R ⁸ , R ¹¹ and R ¹² independently represent a hydrogen atom, a optionally substituted alkyl group or optionally substituted aryl group.

Better still, in formula I, R °, R ¹ , R ² , R ⁵ and R ⁶ represent a hydrogen atom; R ⁴ represents optionally substituted alkyl and, in formula II, R ⁷ , R ⁸ , R ¹¹ , R ¹² are hydrogen atoms and R ⁹ and R ¹⁰ represent a methyl group; R ³ represents H, a methyl group or a phenyl group. According to a second preferred embodiment of the invention, a monomer of formula I as defined above is polymerized with a copolymerizable monomer of formula III:

in which - E is chosen from alkylene optionally substituted and optionally interrupted by one or more divalent groups -Si (A) (B) - where A and B are independently chosen from optionally substituted alkyl or optionally substituted aryl; the divalent group of formula -Ch ¹ -Ar ° -Ch ² - where Ch ¹ , Ch ² independently represent a bond, an oxygen atom, a sulfur atom or -NT-, T being as defined above; and, Ar ° represents optionally substituted arylene; a relationship ; an oxygen atom; the divalent group -NT- in which T represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group; or a chain -Ar ¹ -X ¹ -alk-X ² -Ar ² - where Ar ¹ and Ar ² are independently chosen from optionally substituted arylene, alk represents optionally substituted alkylene and X ¹ , X ² independently represent O or -NT ° -, T ° being as defined above for T;

- R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are independently chosen from a hydrogen atom, an alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyloxy or arylcarbonyloxy group, said group being optionally substituted; it being understood that R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ may also represent 1-alkenyl, and R ¹³ , R ¹⁴ , R ¹⁵ may also represent a polysiloxyl group.

Preferably, the monomers I and or III meet one or more of the following conditions iv) and vi): iv) R ° and R ³ independently represent a hydrogen atom, an optionally substituted aryl group, an alkyl group optionally substituted, R ⁴ represents optionally substituted alkyl or an optionally substituted aryl group, and R ¹ and R ² independently represent an atom hydrogen or an optionally substituted alkyl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group. v) R ¹⁵ and R ¹⁶ are independently chosen from optionally substituted alkyl, optionally substituted aryl and a hydrogen atom; and R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ independently represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group. vi) R °, R ¹ , R ² , R ⁵ and R ⁶ represent a hydrogen atom; R ⁴ represents optionally substituted alkyl and R ³ represents H or phenyl, and, in formula III, R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ are hydrogen atoms; R ¹⁵ and R ¹⁶ represent a methyl group, a phenyl group or a hydrogen atom. vii) X represents an oxygen atom.

According to another particularly preferred embodiment, the compound of formula I is glycidyl methacrylate and the compound of formula III is a divinylbenzene, for example 1,4-divinylbenzene.

Examples of preferred monomers III are:

- 2 - [(N-benzyl-N-methylamino) methyl] -1, 3-butadiene;

- N, N-diallylaniline;

- 2,3-bis (4-ethoxy-4-oxobutyl) -1, 3-butadiene; - 3,7-dimethylocta-1, 6-diene.

The radical polymerization reaction is advantageously carried out in a two-phase medium comprising water and a polar organic solvent to which a very hydrophilic polar compound is added, the role of which is to form stable dispersive systems of suspension or emulsion type. When the polymerization is carried out in suspension, this compound will be chosen from protective colloids such as polyvinylpyrrolidone, polyvinyl alcohols and their ethers, polyethylene glycols and their ethers, polyvinylacetates, polyvinylacetamides, gelatin, methyl cellulose, polymethacrylamides, salts of polymethacrylic acid or the acid itself or phosphates of alkaline earth metals. When the polymerization is carried out in emulsion, this compound will be chosen from a polymer resulting from the polymerization of one of the following ethylenically double-bonded monomers:

where R _x and R _y independently represent hydrocarbyl, it being understood that at least one of R _x or R _y is a fatty hydrocarbyl, having from 8 to 24 carbon atoms. Preferably R _x and R _y are Cι-C ₂₄ alkyl _> better still R _x = CH ₃ and R _y = dodecyl;

where R _z is as defined above for R _x and has from 8 to 24 carbon atoms; preferably R _z represents C10H23;

". CH ₂ =

The polymers which can be used for radical emulsion polymerization and those which can be used for suspension polymerization are in particular described in chapters 6, page 248 and 7, page 290, respectively, of "Radical polymerization in disperse system", J. Barton and I. Capek (Eds), Ellis Horwood series in polymer chemistry, 1994.

Preferably, polyvinylpyrrolidone will be chosen to form a dispersive system suitable for suspension polymerization.

In all cases, the polar organic solvent associated with water can be chosen from optionally substituted aromatic hydrocarbons, halogenated or non-halogenated aliphatic hydrocarbons, ketones, amides, esters, pyridine, propylene carbonate, cyclic ethers or C ₄ -C ₅ cycloalkanols or CrC-is alkanols, without excluding the possibility of using mixtures solvents. The aromatic hydrocarbons are optionally substituted and can be chosen from benzene; xylenes; toluene; ethylbenzene; fluoro-, chloro and bromobenzene; cumene; anisole; benzonitrile; and N, N-dimethylaniline.

As the aliphatic hydrocarbon, there may be mentioned hexane, heptane, ligroin or petroleum ether.

Halogenated aliphatic hydrocarbons which can be used as solvent are in particular methylene chloride, chloroform, carbon tetrachloride and dichloroethane, more preferably carbon tetrachloride and dichloromethane. Ketones suitable as solvent are in particular acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone.

The amides which can be used as solvent are, for example, formamide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidinone, hexamethylphosphorylamide or N-methylpropionamide, the latter being more particularly preferred.

As ester, use will be made, for example, of methyl acetate or better still butyl acetate.

The cyclic ethers that can be envisaged are in particular tetrahydrofuran and dioxane, dioxane being preferred. Alkanols C ₁ -C1 ₈ preferred are for example methanol, ethanol, propanol, isopropanol, butanol, isobutanol and t-butanol.

As the cycloalkanol, cyclohexanol is preferred.

On the other hand, according to another embodiment, the liquefied or supercritical CO ₂ can be substituted for the association of the polar organic solvent and water.

When liquefied or supercritical CO is used as a solvent for polymerization, suitable operating conditions are a pressure of 5 to 40 MPa, preferably from 10 to 35 MPa and a temperature between 30 and 110 ° C.

In order to best determine the operating conditions for radical polymerization, a person skilled in the art can draw inspiration from the following three publications:

• Macromol. Chem. Phys. 2000, 201, No. 13, 1532-1539;

• Journal of Polymer Science, Part A: Polymer Chemistry, vol. 38, 3783-3790, 2000;

- Macromolecules, 2000, 33, 6757-6763. However, the invention is not limited to these embodiments and also includes the processes in which the radical polymerization is carried out without solvent or in a single-phase medium. In this case also, the solvent is chosen from optionally substituted aromatic hydrocarbons, halogenated or non-halogenated aliphatic hydrocarbons, ketones, amides, pyridine, propylene carbonate, cyclic ethers, C ₄ -C ₈ cycloalkanols or C-ι-Cι ₈ alkanols, without excluding the possibility of using solvent mixtures.

Radical polymerization in suspension in a two-phase water / organic solvent medium is particularly favorable if it is desired to obtain a polymer in the form of porous beads, which is particularly advantageous in the case of certain applications such as synthesis on a solid phase, immobilization of enzyme and chiral chromatography.

On the other hand, in order to adapt the physical and physicochemical properties of the polymer beads (such as appearance, porosity, specific surface, size of the beads and resistance), it is recommended to add to the medium reaction of the radical polymerization of additives or cosolvents.

The size will for example depend on the quantity and the nature of the additive used.

More particularly, with a view to improving the porosity properties of the polymer beads, it is recommended to add to the reaction medium a C ₅ -C ₈ cycloalkyl alcohol on the one hand and a CiC-is alkanol on the other hand , these functioning as porogenic solvents.

Cycloalkyl alcohol is generally an alcohol capable of dissolving the polymer, such as cyclohexanol. The alcohol in Cι-Cι ₈ is especially chosen from dodecanol, lauryl alcohol, methanol, ethanol, propanol, butanol, octanol, decanol, tetradecanol or hexadecanol. Advantageously, the CiC-is alcohol is dodecanol or lauryl alcohol. As the preferred pore-forming medium, a mixture of cyclohexanol and dodecanol or a mixture of cyclohexanol and lauryl alcohol will be used.

In order to control the parameters of the macroporous structure of the polymers of the invention, such as the specific surface of the beads, their diameter, the pore volume, the heat resistance, the resistance to alkaline solutions, the dynamic capacity, the selectivity , the equilibration rate and the content of epoxy groups, it is also possible to influence the speed of stirring of the reaction medium, the concentrations of the various reagents in the medium, the temperature and the polymerization times. For an adequate adaptation of the reaction conditions, the person skilled in the art will refer for example to one or more of the following publications:

- Biotechnology and bioengineering, vol. 48, no.5 (5), 1995, 476-480;

- Angew. Makromol. Chem. 1975, 708, 135-143;

- Angew. Makromol. Chem. 1981, 95, 109-1 15; - Materials Science Forum, 214, 1996, 155-162; and

- Angew. Makromol. Chem. 1981, 95, 117-127.

The anionic polymerization is generally carried out in a single-phase organic solvent chosen from aliphatic, cyclic, saturated or aromatic hydrocarbons; ethers, pyridine and mixtures thereof.

Generally, the hydrocarbons are hexane, heptane, benzene, toluene or xylenes.

Among the preferred hydrocarbons, heptane, cyclohexane or toluene will be selected. The ethers which can be used as solvents are, for example, diethyl ether, diisopropyl ether, tetrahydrofuran or dioxane, diethyl ether and tetrahydrofuran being preferred. Particularly suitable mixtures of these solvents are the toluene / tetrahydrofuran mixture and the cyclohexane / diethyl ether mixture.

The anionic polymerization temperature is generally between -100 ° C and 0 ° C, preferably between -60 ° C and -30 ° C, better still between -50 ° C and -35 ° C.

For further information on the operating conditions suitable for carrying out the anionic polymerization, those skilled in the art are invited to refer to the following documents:

- G. Hild, J.P Lamps, Polymer, vol 36, 1995, 4841; and - Prog. Polym. Sci. 24 (1999) 793-873, P. Vlcek, L. Lochmann.

The compounds of formulas I and II in racemic form are commercially available, or easily prepared by a person skilled in the art by using conventional methods of organic chemistry.

The optically active compounds of formula I can be prepared from the corresponding racemic mixtures either by chemical resolution, or by enzymatic resolution, or by chiral chromatography.

For the enzymatic duplication, a person skilled in the art can draw inspiration from the work of W.E. Ladner, G. M. Whitesides described in J. Am. Chem. Soc. 1984, 106, 7250-7251. The principle of the method illustrated in this document is based on the selectivity of the enzyme used, a lipase, for the hydrolysis of esters of epoxide alcohols. Only one of the enantiomers of the ester to be hydrolyzed is attacked by the lipase so that at the end of the hydrolysis reaction, an optically active alcohol and one of the enantiomers of the ester to be hydrolyzed are isolated. departure, one that is not attacked by lipase.

The conditions for the hydrolysis reaction will be easily determined by a person skilled in the art depending on the enzyme used.

Generally, the reaction is carried out in an aqueous medium with control of the pH of the reaction medium. Schematically, when X = O and n = 1 in the compound of formula

I, the reaction can be represented as follows: lipase

optically active optically active

Although in the previous diagram the chirality of each of the products obtained has been indicated, it should be understood that this chirality can be reversed, the only constant being that the enantiomeric ester has the configuration opposite to that of the ester actually hydrolysed by lipase.

As a variant, and with a view to achieving catalytic duplication of the racemic of the compounds of formula I, a person skilled in the art may refer to the work of M. Tokunaga, JF Lanow, F. Kakiuchi, EN Jacobsen, Science, 1997, 277, 936-938.

This publication illustrates in particular the stereoselective hydrolysis of the epoxide function of the ester of formula I. The stereoselectivite results from the incorporation into the reaction medium of a catalyst, a metal complex of cobalt, which catalyzes the hydrolysis reaction of only one of the enantiomers of the racemic mixture of the ester of formula I.

The catalyst (Cat.) Exemplified in this publication has the formula:

The hydrolysis reaction of the epoxide function of an ester of formula I in which X = O can be diagrammed as follows:

Again, the chirality of each of the products obtained as shown in the previous diagram could be reversed, the main thing being that the enantiomer of formula I isolated has a configuration opposite to that of the hydrolyzed enantiomer.

Another variant consists in diastereoselectively synthesizing the optically active epoxide of formula I.

To do this, those skilled in the art can draw inspiration from known methods.

When X represents O, a person skilled in the art can prepare the compounds of formula I by reaction of the corresponding, optically pure, epoxy alcohol of formula VIII:

in which n, R ° to R ³ and * are as defined above for formula I, on the appropriate acid of formula IX:

in which R ⁴ to R ⁶ are as defined above for formula I, or an activated form thereof, under mild conditions of esterification and preferably in basic or neutral medium. When an acid of formula IX with a free -COOH function is used, it is desirable to carry out the esterification in the presence of a condensing agent such as for example a carbodiimide, optionally in the presence of an activating agent such as for example, hydroxybenzotriazole or hydroxysuccinimide, with intermediate formation of dialkyl- or dicycloalkyl-O-ureides. Representative condensing agents are dicyclohexyl- and diisopropylcarbodiimides and carbodiimides soluble in an aqueous medium.

The compounds of formula IX are marketed or easily prepared by a person skilled in the art from suitable commercial compounds.

The activated derivatives of acids of formula IX have for example the formula -CO-T where T is an activating group. Preferred activating groups are well known in the art, such as, for example, halogen (chlorine or bromine), azide, imidazolide, p-nitrophenoxy, 1-benzotriazole, ON-succinimide, acyloxy and, more particularly, pivaloyloxy, alkoxycarbonyloxy such as, for example, C ₂ H ₅ OCO-O-, dialkyl- or dicycloalkyl-O-ureide. A series of suitable methods for the preparation of activated derivatives of carboxylic acid is proposed by J. March in Advanced Organic Chemistry, ed. John Wiley & Sons.

The optically pure compounds of formula VIII can be obtained by asymmetric epoxidation of the corresponding allyl alcohols of formula X:

in which n, R ° to R ³ are as defined above for formula VIII, it being understood that X represents either the E isomer or the Z isomer. The conditions of this asymmetric epoxidation reaction are in particular described by Y-Gao, RM Hanson, JM Klunder and co., In J. Am. Chem. Soc. 1987, 109, 5765-5780. They involve the cold action of tert-butylhydroperoxide and the presence of Ti (O-iPr) ₄ where iPr represents isopropyl as well as the presence of (+) - or (-) - diethyl tartrate or (+) - or (-) - diisopropyl tartrate. The reaction can be carried out in a polar aprotic solvent such as a halogenated aliphatic hydrocarbon (and for example dichloromethane) at a temperature of -50 to 0 ° C, preferably from -30 to -10 ° C. The amount of epoxide functions incorporated into the polymer is easily determined by a person skilled in the art by dosing with periodic acid.

More specifically, the polymer of the invention is treated in an acid medium so as to cause the opening of the epoxide functions into diol-1, 2 functions. Then, the resulting polymer is reacted with an excess of periodic acid. This treatment leads to the transformation of the diol-1,2 functions into aldehyde functions according to the scheme:

HIO ₄ + (£) - CH-CH— © 0_CHO + © - CHO

OH OH

+ HIO ₃ + H ₂ O where (P) and (P ^) represent fractions of said polymer. HIO ₃ and HIO ₄ are then reduced by K1 according to the reactions: HIO3 + 5KI + 2H ₂ O → 3I ₂ + 5KOH HIO4 + 7KI + 3H ₂ O - »4I ₂ + 7KOH.

The determination of the iodine released by the thiosulfate according to the reaction: 2Na ₂ S ₂ O ₃ + l ₂ - Na ₂ S ₄ O ₆ + 2Nal allows a determination of the excess of periodic acid used and indirectly of the amount of epoxy functions initially present in the polymer.

The invention further relates to the optically active polymer obtainable by regiospecific stereoselective reaction of a nucleophilic agent on the polymer of the invention with epoxide functions as defined above, whereby the partial regiospecific stereoselective opening is caused or total of the epoxy functions of said reactive polymer. The optically active polymer resulting from the attack of a nucleophilic agent is designated "modified polymer" in the following.

Preferably, the action of said nucleophilic agent causes the opening of all of the epoxy functions. Suitable nucleophilic agents are those comprising as nucleophilic site a halogen atom, an oxygen atom, a sulfur atom, a carbon atom, a nitrogen atom, a phosphorus atom or a selenium atom.

The nucleophilic agent and the operating conditions are more precisely chosen so as to cause the opening of the epoxy functions with conservation of the chirality of at least one asymmetric center. In this way, the resulting modified polymer is also optically active. Conditions more particularly suitable for this purpose are in particular a basic or neutral medium. The opening reaction of epoxides by the action of a nucleophile is more precisely described in the following works and publications:

- J. March, Advanced Organic Chemistry "Reactions, mechanism and structure", 4 ^th Ed. 1992, J. Wiley & Sons, p. 368;

- R.J. Gritter, The chemistry of functional groups, "The chemistry of ether linkage", S. Patai (Ed.) 1967, Interscience, p. 390-41 1 and references cited;

- G. H. Posner, Angew. Chem. Int. Ed. Engl. 1978, 17, 487-496; and

- FA Carey, RJ Sundberg, "Advanced Organic Chemistry", Part B, Reactions and Synthesis, 2 ^nd ed., 1983, Plénum Press (Ed.) P. 498.

By way of example, the nucleophilic agent can be an amine (and in particular a diamine) or a hydroxyamine. As nucleophilic amine, a primary or secondary aliphatic amine, a (hetero) aromatic amine or a cyclic amine may be used. More generally, an aliphatic, aromatic and / or cyclic amine may be used, that is to say an amine having an aliphatic part and / and / or a (hetero) aromatic and / or cyclic part. Preferably, the nucleophilic amine has the formula HNR ^d R ^e where R ^d and R ^e are independently chosen from an optionally substituted saturated, linear or branched aliphatic hydrocarbon chain; an optionally substituted saturated carbocyclic group; an (hetero) aromatic group, optionally substituted; a hydrogen atom; and a radical comprising a saturated hydrocarbon aliphatic chain, linear or branched, and a carbocyclic part, saturated and / or (hetero) aromatic, said radical being optionally substituted. By saturated aliphatic hydrocarbon chain is meant a linear or branched alkyl group as defined above or, when it is a radical comprising an aliphatic chain, the corresponding linear or branched saturated alkylene group.

By saturated carbocycle is meant a cycloalkyl radical as defined above. By carbocyclic part is meant the corresponding cycloalkylene radical.

By (hetero) aromatic is meant an aromatic carbocyclic radical or a heteroaryl radical.

The aromatic carbocyclic radicals are as defined above. By heteroaryl is meant a mono- or polycyclic aromatic heterocycle comprising one or more heteroatoms chosen from O, N and S. When the heteroaryl is polycyclic, then it is composed of monocyclic rings which are either aromatic heterocyclic or aromatic carbocyclic such as defined above since at least one of said monocyclic rings constituting it is aromatic heterocyclic. In heteroaryl, the monocyclic nuclei constituting the heteroaryl are attached two by two by a simple carbon-carbon bond and / or condensed to each other.

Preferably, the heteroaryl is composed of one or more 5- to 7-membered, preferably 5 to 6-membered, monocyclic rings. The heteroaryl is preferably chosen from furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, indolyl, isoindolyl, benzo-benzoluryl, benzolurol, benzol , cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl and pteridinyl.

The aliphatic chains and the carbocycles described above are optionally substituted. The substituents carried by these radicals are chosen so as not to react with the epoxy functions of the polymer and more generally with the reactants present under the reaction conditions.

Suitable substituents are the alkoxy substituents; alkyl; aryl; heteroaryl; aryloxy; cycloalkyl; cycloalkyloxy; cyano; nitro; halogen; oxo; amino disubstituted by alkyl, aryl and or cycloalkyl; -CONR ^a R ^b in which R ^a and R ^b are independently selected from H, alkyl, aryl and cycloalkyl; -COOR ^f where R ^f is as defined for R ^a .

In addition, it will be noted that each of the radicals R ^d and R ^e of the nucleophilic amine can carry one or more other optionally substituted amino and / or hydroxy functions.

Other nucleophilic amines are secondary heterocyclic amines in which the nucleophilic site -NH- is endocyclic. Said heterocyclic amine is either monocyclic or polycyclic and optionally comprises, in addition to said function -NH-, one or more other heteroatoms such as O, N and S. The heterocyclic amine is saturated or unsaturated. In the latter case, it may include one or more ethylenic unsaturations.

Heterocyclic amines consist of one or more monocyclic nuclei, said monocyclic nuclei each preferably having from 5 to 7 links and being either linked to each other by simple carbon-carbon bonds, or condensed two by two.

More particularly preferred examples of amines are aliphatic amines, aliphatic diamines, arylalkylamines, aminopyridines, aminoalkylpyridines, aminoquinolines, aminoalkylquinolines, heterocyclic amines in which the nucleophilic site is -NH- such as mono heterocyclic amines - and bicyclic comprising as sole heteroatoms 1 to 5 nitrogen atoms. A particular example of a heterocyclic amine is as follows:

In the case of primary or secondary amines, a process consists in reacting the polymer with epoxy functions with 1 to 5 equivalents of the amine nucleophile, preferably 2 to 4 equivalents, the equivalents being expressed relative to the number of moles of epoxide functions present in the polymer.

The reaction temperature depends on the strength of the nucleophilic agent.

Generally, it is preferable to heat the reaction medium to a temperature between 50 and 150 ° C, preferably between 80 and 120 ° C.

When the nucleophilic agent is an amine, the resulting modified polymer carries β-hydroxyamine functions:

It will be designated polyaminoalcohol in the following. The nucleophilic agent generally attacks the epoxy functions of the polymer of the invention on the least congested side, that is to say on the side most distant from the polymer backbone. The conditions of the nucleophilic attack are determined by a person skilled in the art with a view to obtaining the opening of each of the epoxy functions with retention of the configuration at at least one of the asymmetric centers of said epoxy function.

The nucleophilic agent is chosen according to the application envisaged. Other suitable nucleophiles are described in Synthesis, 1984, 9, 629-656; J. Org. Chem. 40, 1975, 375-377; J. Am. Chem. Soc. 1953, 75, 1636; and Angew. Chem. Int. Ed. Engl. 1978, 17, 487-496. Among these, we will notably mention:

- hydroxy-functional nucleophiles (such as water, alcohols and in particular alkanols in CIC-IO, aromatic alcohols in Cβ-Cis and arylalkyl alcohols where the alkyl part is in CIC-IO and the aryl part is C ₆ -Cιs);

- the thiol nucleophiles (such as mercaptans including thiols of formula -SH ° M wherein M ⁰ is for example a C1-C _10, an aryl group having ₆ -Cι _8; or a group (C ₆ -Ci ₈ ) aryl- (CrCιo) alkyl);

- Nucleophilic agents with -SeH function (such as selenomercaptans and in particular selenols of formula M ° -SeH where M ° is as defined above);

- Carboxylic acids with -COOH function and in particular the acids of formula M ° -COOH where M ⁰ is as defined above; - sulfite and bisulfite anions;

- Silylated halides of general formula XSiM ¹ M ² M ³ where X is a halogen atom, M ¹ , M ² and M ³ represent optionally substituted hydrocarbon radicals and are for example as defined for M ⁰ above;

- Silylated sulfides of general formula MS-SiM ¹ M ² M ³ where M, M ¹ , M ² and M ³ represent optionally substituted hydrocarbon radicals and are in particular as defined for M ° above;

- Silylated selenides of general formula M ⁴ -Se-SiM ¹ M ² M ³ where M ⁴ , M ¹ , M ² and M ³ represent optionally substituted hydrocarbon radicals and are in particular as defined for M ⁰ above;

- Silylated cyanides of general formula NC-SiM ¹ M ² M ³ where M ¹ , M ² and M ³ represent optionally substituted hydrocarbon radicals and are for example as defined for M ⁰ above; - the tris (hydrocarbylselenyl) boranes of general formula B (Se-M ') ₃ where M' represents an optionally substituted hydrocarbon radical and is for example as defined above for M ⁰ ;

- the tris (hydrocarbylthio) boranes of general formula B (S-M ') ₃ where M' represents an optionally substituted hydrocarbon radical and is for example as defined above for M ⁰ ;

- the trihydrocarbylstannyllithium of general formula (M ') ₃ SnLi where M' represents an optionally substituted hydrocarbon radical and is for example as defined above for M ⁰ ;

- the carbanions from magnesians such as those of formula M'-MgX where M 'represents an optionally substituted hydrocarbon radical and is for example as defined above for M ⁰ ;

- the carbanions from organomagnesians of formula (M '^ Mg where M' represents an optionally substituted hydrocarbon radical and is for example as defined above for M ⁰ ; - the carbanions from hydrocarbyllithians of general formula M'Li where

M 'represents an optionally substituted hydrocarbon radical and is for example as defined above for M ⁰ , the nucleophilic attack being used in this case in the presence of copper salts; - the carbanions derived from homocuprates of general formula M 'CuLi where M' and M "independently represent an optionally substituted hydrocarbon radical and are, for example, as defined above for M ⁰ ;

- carbanions from mixed cuprates of general formula (M'CuCN) Li where M 'is as defined above;

- the carbanions from mixed cuprates of general formula M'M "Cu (CN) Li ₂ where M 'and M" independently represent an optionally substituted hydrocarbon radical and are, for example, as defined above for M ⁰ ; - the nucleophilic agents of general formula M'-C≡CLi where M 'is as defined above for M ⁰ , the nucleophilic attack being used in this case in the presence of copper salts:

- carbanions derived from malonates of general formula M'OOC-CH ^" - COOM" where M 'and M "are as defined above. Preferred nucleophilic agents are amines, guanidines, morpholines, and hydroxylamines.

The modified polymer of the invention is optically active. It is particularly useful as a stationary phase in chiral chromatography, whether in preparative chromatography or in analytical chromatography. For such use, the nature of the nucleophilic agent is not critical. However, it is preferred that the nucleophilic agent is an aliphatic or aromatic amine. Said polymer has modular physical properties, which makes it possible to improve the performance of the polymer material and in particular the separation efficiency. The modulation of the properties of the modified polymer is carried out during the synthesis of the polymer with epoxy functions as taught previously.

The invention therefore relates to the use of a modified polymer resulting from the attack of a nucleophilic agent on the polymer with epoxy functions of the invention, as described above, as a polymer matrix usable in chiral chromatography.

It is also possible to graft the polymer of the invention on a support conventionally used in chromatography such as, for example, silica or alumina, before its use in chromatography. For the grafting, a person skilled in the art will use the conventional techniques known in the technique recommended for the modification of silicas and aluminas. With a view to grafting, it is desirable to react the appropriately functionalized silica or alumina with the modified polymer of the invention. Appropriate methods for grafting are as described in:

- Reactive and Functional Polymers, 1997, 153;

- Solid State lonic, (1999), 29;

- Tetrahedron: Asymmetry, (2000), 2183;

- M.A. Brook, Silicon in Organic Organometallic and Polymer Chemistry: chapter 10, p. 309, J. Wiley, 1999;

- Hydrid organic-inorganic composites, J.E. Mark, C. Y-C. Lee and P.A. Bianconi (Eds) 1995; ACS symposium series 585, chapters 8, 10, 11, 19 and 26.

The invention therefore relates, according to another of its aspects, to a polymeric material usable as a stationary phase in chiral chromatography which can be obtained by grafting reaction of the modified polymer of the invention on a conventional support used in chromatography, chiral or non-chiral, such as silica or alumina.

Said modified polymer is also suitable for use:

• in solid phase synthesis, the modified polymer playing the role of chiral auxiliary;

• in asymmetric catalysis, either as a chiral inducer or as a chiral ligand of a transition metal with a view to the preparation of metal catalyst complexes.

The modified polymers of the invention are more particularly useful in the catalysis of reactions for reducing carbonyl functions, activated or not, or of reactions involving the formation of C-C bonds.

According to a first embodiment of the invention, the modified polymers of the invention are used as iigands for the preparation of metal complexes intended for asymmetric catalysis. In this case, the coordinating metal is a transition metal chosen from rhodium, ruthenium, iridium, nickel, cobalt, palladium and platinum.

More specifically, when the opening of the epoxy functions of the polymers of the invention has been carried out by the action of an amine-type nucleophile as described above, the resulting modified polymer has β-hydroxy-amine functions and can be used directly as a ligand for the preparation of metal complexes. This polymer will be designated polyamino alcohol in the following. Alternatively, the modified polymer can be chemically transformed again before the preparation of the metal complex. The modified polymers of the invention can also be used as they are or after further chemical transformation as an asymmetric inducer in reactions for reducing carbonyl groups and / or in reactions involving the formation of CC bonds. As an example, we could draw inspiration from the work described in Tetrahedron

: Asymmetry, 1997, 8, 2881 and Tetrahedron: Asymmetry, 1997, 8, 1083 and transform the β-hydroxy-amine functions of the modified polymers described above into amidophosphine-phosphinite functions of formula:

or aminophosphine-phosphinite of formula:

Thus transformed, the modified polymers of the invention can be used as ruthenium (II) ligands for the preparation of complexes which can be used in the asymmetric hydrogenation of α-ketoesters or β-ketoesters. Another possibility consists in transforming the β-hydroxyamine functions of the modified polymers into oxazaborolidine or phosphoramidate functions of the formula:

In accordance with the work of: - J. Chem. Soc. Chem. Commun, 1981, 315;

- Angew. Chem. Int. Ed. Engl. 1996, 35, 1992; - Asymmetry, 1994, 5, 1211;

- Tetrahedron: Asymmetry, 1994, 5, 165;

- Tetrahedron Lett. 1993, 34, 3243; - Tetrahedron: Asymmetry, 1997, 8, 1259;

- J. Am. Chem. Soc. 1996, 118, 10938;

- Tetrahedron: Asymmetry, 1997, 8, 277; - Tetrahedron Lett. 1998, 39, 1705;

The polymers modified with oxazaborolidine or phosphoramidate functions can be used as such as catalysts in the asymmetric reduction of various ketones such as aliphatic and / or aromatic ketones, the aliphatic ketones being saturated or unsaturated (the unsaturations being ethylenic or acetylenic). This will be done for example for the reduction of aliphatic ketone or benzophenones to corresponding secondary alcohols.

In addition, the reduction of α-ketoester or β-ketoesters to corresponding α- or β-hydroxyesters can be carried out in accordance with the work of Chem. Rev. 1992, 92, 935 in the presence of a modified Pt Al ₂ θ ₃ catalyst. In the context of the invention, a PI / AI ₂ O ₃ catalyst will be used for this reaction comprising, as ligand, a modified polymer of the invention, with β-hydroxylamine functions (polyaminoalcohol).

The modified polymers of the invention with β-hydroxylamine functions (polyaminoalcohols) can also be used as ligands of ruthenium II complexes to catalyze the asymmetric reduction of aromatic ketones, cyclic and / or aliphatic by hydride transfer. This type of reaction is illustrated in particular in:

- J. Chem. Soc. Chem. Common. 1996, 233;

- J. Org. Chem. 1997, 62, 5226; and - J. Org. Chem. 1998, 63, 2749.

Another type of reaction catalyzed by nickel and cobalt complexes prepared using as ligands the modified polymers of the invention with β-hydroxylamine functions (polyamino alcohols) are Michael type addition reactions such as those illustrated in: - Tetrahedron: Asymmetry, 1997, 8, 1467; and

- Tetrahedron: Asymmetry, 1997, 8, 1377, which relate more precisely to the addition of dialkyl-zinc or diaryl-zinc to α, β-ethylenic ketones.

The modified polymers of the invention with β-hydroxylamine functions (polyamino alcohols) can also be used as an asymmetric inducer in the addition of dialkyl- or diarylzinc on aldehydes. For this type of reaction, we could refer to the work of:

- Chem. Rev. 1992, 833;

- Angew. Chem. Int. Ed. Engl. 1991, 30, 49; and - Chem. rev. 2000, 100, 2159-2231.

Likewise, the modified polymers of the invention with β-hydroxylamine functions (polyamino alcohols) can be used as asymmetric inducer in the addition reactions of dialkylzinc or of diarylzinc on ketones (cf. J. Am. Chem. Soc. 1998, 120, 12157). For the implementation of this method, a person skilled in the art can draw inspiration from the work of Pericas et al. described in J. Org. Chem. 1998, 63, 6309, as well as to the following publications:

- Tetrahedron: Asymmetry, 1997, 8, 1529; and - Angew. Chem. Int. Ed. Engl. 1996, 35, 642.

The polymers modified with β-hydroxylamine functions (polyamino alcohols) used for one of the applications in the asymmetric catalysis described above result more specifically from the attack on the epoxy functions of a polymer according to the invention by a nucleophilic agent. chosen from a arylalkylamine (especially benzylamine); an (arylalkyl) (alkyl) amine, especially (benzyl) (methyl) amine; and a heterocyclic amine of formula:

The complexes comprising a modified polymer of the invention and a transition metal can be prepared according to the known methods described in the literature.

For the preparation of ruthenium complexes, reference may be made in particular to the publication by J.-P. Genêt [Acros Organics Acta, 1, Nr. 1, pp. 1-8 (1994)] and for the other complexes, to the article by Schrock R. and Osborn J.A. [Journal of the American Chemical Society, 93, pp. 2397 (1971)].

In general, the complexes of the invention can be prepared by reacting the modified polymer of the invention with a precursor based on the desired transition metal, in an appropriate organic solvent. The reaction is carried out at a temperature between room temperature (15 to 25 ° C) and the reflux temperature of the reaction solvent.

As examples of organic solvents, there may be mentioned, inter alia, aliphatic hydrocarbons, halogenated or not, and more particularly hexane, heptane, isooctane, decane, benzene, toluene, methylene chloride, chloroform; solvents of ether or ketone type and in particular diethyl ether, tetrahydrofuran, acetone, methyl ethyl ketone; alcohol type solvents, preferably methanol, ethanol or isopropanol; and amide solvents such as formamide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidinone or hexamethylphosphorylamide, dimethylformamide being the preferred amide.

The catalytic complexes based on rhodium, iridium and ruthenium are for example obtained from a precursor prepared in situ or preformed by the addition of 1 to 10, preferably from 1 to 2 equivalents of the modified polymer of the invention ( designated polymer P below). In the case of rhodium, iridium and ruthenium the precursors can be salts of formula MX ₃ in which X can represent a halide or a nitrate and M represents Rh, Ir or Ru respectively. Alternatively, the precursor used for the synthesis of catalytic complexes is a complex designated precursor complex in the following.

In the case of iridium and rhodium, the precursor complexes, known to those skilled in the art, can be defined by the following formula:

[MeX ° L ₂ ] ₂ in which Me represents iridium or rhodium; L represents a ligand of type π, in particular CO, ethylene or a monoolefin, or else L ₂ represents a bidental ligand of type π such as an acyclic diene for example hexadiene or cyclic for example cyclooctadiene or norbornadiene ; X ° represents a bridging ligand such as for example a halo (Cl, Br, I), a thiolato, an alcoholato, a hydroxy.

As an example of precursor complexes in the case of rhodium, the Cramer complex, [Rh (cod) CI] ₂ , [Rh (nbd) CI] ₂ , [Rh (CO) ₂ CI] ₂ , Rh (C ₂ H ₄ ) ₂ (acac), Rh (CO) ₂ (acac), [lr (cod) CI] ₂ , [lr (nbd) CI] ₂ , lr (C ₂ H ₄ ) ₂ (acac) and lr ( CO) ₂ (acac), where cod represents cyclooctadiene; nbd represents norbornadiene; and acac represents acetylacetonate. Other precursor complexes in the case of rhodium and iridium have the formula:

[MeL ₄ ] X ¹ in which Me represents iridium or rhodium; L represents a ligand of type π, in particular ethylene, a monoolefin or CO; or L ₂ represents a bident ligand of type π such as a diolefin; X ¹ represents a non-coordinating anion of the PFβ ^" , PCIβ ^" , BF ₄ ^" , BCI ₄ ^" , SbFβ ^" , SbClβ ^" , BPh ₄ ^" , CIO4 ^{" type} ,

CF ₃ SO ₃ ^" .

As an example of such precursors, mention may be made of Rh (cod) ₂ BF and lr (cod) ₂ BF ₄ where cod represents cyclooctadiene. In the case of ruthenium, the precursor complexes known to those skilled in the art can be defined by the following formula:

[RuL ₂ X ² ₂ ] ₂ in which L represents a ligand of type π, in particular CO, ethylene or a monoolefin; or L ₂ represents a bident ligand of type π and for example an acyclic diene such as hexadiene or a cyclic diene such as cyclooctadiene or norbornadiene; X ² represents a bridging ligand such as for example a halo (Cl, Br, I), a thiolato, an alcoholato, a hydroxy.

As examples of such precursor complexes, mention may be made of [Ru (cod) Cl2] 2 where cod represents cyclooctadiene.

As other precursor complexes, mention may be made of the complexes of formula [RuL2X ² ] 2 where L and X ² are as defined above for [RuL ₂ X ² ] 2- As an example, mention may be made of [Ru (CO) 2CH ₃ COO] ₂ .

Other precursor complexes in the case of ruthenium have the formula: RuX ³ ₂ L ₄ , where L represents a ligand of type π, in particular CO, ethylene or a monoolefin, or else L ₂ represents a bidental ligand of type π and for example an acyclic diene such as hexadiene or a cyclic diene such as cyclooctadiene and norbornadiene; or L ₃ represents a trident ligand of type π such as an arene functionalized or not; X ³ represents a bridging ligand such as for example a halo (Cl, Br, I), a thiolato, an alcoholato, a hydroxy.

Examples of such precursor complexes are Ru (C ₁ ιH ₁₉ θ ₂ ) ₂ (C ₈ Hι ₂ ) and [Ru (benzene) CI ₂ ] ₂ .

This list is not exhaustive and the person skilled in the art may draw inspiration for example from the metal precursors described in Comprehensive Organometallic Chemistry, G. Wilkinson, F.G.A. Stone and E.W. Abel (Eds), Pergamon Press, 1982 and Comprehensive Organometallic Chemistry II, R.J. Puddephatt, E.W. Abel, F.G.A. Stone and G. Wilkinson (Eds), Pergamon Press / Elsevier, 1995 and those described in Comprehensive Coordination Chemistry, G. Wilkinson, RD Gillard and JA McCleverty (Eds), Pergamon / Elsevier, 1987. Similarly, he can find the know-how enabling it to form new complexes derived from polymers of the invention described above.

The complexes of ruthenium II with a modified polymer according to the invention, with β-hydroxylamine functions (polyamino alcohols) are more particularly suitable for the asymmetric catalysis of reduction reactions of carbonylated functions by hydride transfer.

Thus, according to another of its aspects, the invention relates to the metal complex of a transition metal comprising, as a ligand, a polymer of the invention or a modified polymer obtained by the action of a nucleophilic agent on a polymer of the invention, whereby the epoxy functions are opened.

Advantageously, the transition metal in this complex is ruthenium, iridium or rhodium, preferably ruthenium. Examples of ketones which can be selected as substrate for reduction reactions by hydride transfer more preferably correspond to formula C:

in which: - R ¹ is different from R ^j ,

R ¹ and R ^j represent a hydrocarbon radical having from 1 to 30 carbon atoms optionally comprising one or more functional groups,

- R 'and R ^J may form a ring optionally comprising another heteroatom, - Z is or comprises a heteroatom, oxygen or nitrogen or a functional group comprising at least one of these heteroatoms.

A first preferred group of such ketone substrates has the formula D:

R i ^ RJ

in which :

- R 'is different from R ^j , the radicals R' and R ^j representing a hydrocarbon radical having from 1 to 30 carbon atoms, optionally substituted, and optionally comprising another ketone and or acid function, ester, thioacid, thioester;

- R 'and R ^j can form a carbocyclic or heterocyclic ring, substituted or not, having 5 to 6 atoms. Examples of particularly suitable substrate ketones are acetophenone, (phenyl) (trifluoromethyl) ketone, α-keto esters and β-keto esters.

The reduction of ketones by hydride transfer is carried out in a conventional manner using the metal complexes of the invention described above as catalyst.

The reduction is carried out in basic medium, for example in the presence of an organic base such as an alkali metal alkoxide and ^more particularly BuOK or an inorganic base such as NaOH, KOH, NaHCO 3, Na ₂ CO _3, KHCO ₃ and K ₂ CO ₃ .

The reduction is carried out in the presence of a hydrophilic polar organic solvent such as an aliphatic alcohol lower in CrC ₁₀ (for example methanol, ethanol, propanol, isopropanol, butanol, t-butanol) , a cycloalkanol (such as cyclohexanol), or methylcellosolve. The reaction temperature is generally maintained between room temperature (15-30 ° C) and the reflux temperature of the solvent, generally up to 150 ° C.

The conditions for the reduction will be easily developed by a person skilled in the art, for example with reference to Tetrahedron Lett. 1995, 36, 8776, Bull. Soc. Chim. Fr. 1994, 13, 600 and Chem. Rev., 1985, 85, 129.

The invention therefore more generally relates to the use of a modified polymer as a ligand optionally after transformation into oxazaborolidine or phosphoramidate in the preparation of transition metal complexes or as a chiral inducer, in stereoselective catalysis. Said complexes are more particularly suitable for catalyzing the stereoselective reduction of carbonyl and imine functions or for catalyzing reactions involving the formation of C-C bond.

The polymers with epoxy functions of the invention can also be used as polymeric material for the immobilization of enzymes. The immobilization of enzymes on solid supports provides practical advantages for the implementation of biocatalytic processes. Among these advantages, the ease of separation of the reaction medium is a major advantage allowing the recycling of the material. The reactivity of the polymers of the invention with an epoxide function allows easy grafting of the enzyme to the polymer backbone via the hydroxyl, thiol and / or amino functions of the enzyme.

As a variant, it is possible to immobilize the enzymes on the modified polymer of the invention resulting for example from the nucleophilic attack of a diamine on the polymer with epoxide functions of the invention.

To do this, it suffices for example to react said modified polymer with glutaraldehyde before reacting it with the enzyme to be immobilized.

To do this, the skilled person will refer for example to Adv. Mater. 1999, 11, 1 169-1 181.

The invention therefore also relates to the use of a polymer with epoxy functions or of a modified polymer according to the invention as polymer material for the immobilization of enzymes.

According to another of its aspects, the invention relates to the use of a modified polymer of the invention as defined above as polymer support in synthesis on solid phase.

The invention is more precisely illustrated below with the aid of the following examples.

In Examples 4.1 to 4.6, 10.1 to 10.3, 11 and 15, the functionalization rate, (f) is the maximum number of moles of nucleophile introduced per gram of polymer. It is more precisely defined by the formula f = f0 / (1 + f0 x PM / 1000)), where fO represents the number of epoxide functions per gram of initial monomer with epoxide function and PM the weight of the nucleophile.

EXAMPLE 1

Preparation of optically pure glycidyl methacrylate by enzymatic resolution

To 10 g of glycidyl methacrylate (70.3 mmol) dissolved in 80 ml of double distilled water are added, with stirring, 10 g of lipase (EC 3.1.1.3, sigma type II from pig pancreas). The pH is maintained at 7.8 by adding sodium hydroxide (1.4 mol / l) using an automatic burette (measuring the pH using a pH meter and a double electrode glass - calomel), which allows to follow the progress of the reaction. After 24 h (conversion: 57%), the reaction mixture is filtered through a No. 3 sintered glass covered with 300 g of silica. The silica is washed with 300 ml of technical dichloromethane. The organic phase is concentrated (30 ml) and washed with a saturated aqueous sodium bicarbonate solution (25 ml), then with deionized water (2 times 15 ml). After drying over a sodium sulfate / sodium bicarbonate mixture (90/10) and then evaporation, 3.11 g of glycidyl methacrylate (21.9 mmol) are obtained. Yield: 31.2% Enantiomeric excess of (glycidyl RJ-methacrylate: 70% ([α] o ²⁵ = -20.6; c ≈ 0.564, CH ₂ CI ₂ ).

EXAMPLE 2

Preparation of optically pure glycidyl methacrylate by chemical splitting

A 0.457 g (0.668 mmol) of (1R, 2R) - (-) - 1, 2-diaminocyclohexane-N, N'- bis (3,5-di-tetιf-butylsalicylidene) cobalt (II) dissolved in 12 ml of technical toluene are added 76 μl (1.336 mmol) of 99.8% acetic acid, while stirring. After one hour at room temperature, the solvent is evaporated. At 0 ° C., to the black residue obtained are added 19 g (133 mmol) of racemic glycidyl methacrylate, then, drop by drop, 1.20 g (66 mmol 0.55 eq.) Of deionized water. The reaction mixture is allowed to return to room temperature. After 24 hours, the (R) -glycidyl methacrylate transformed into a diol is separated from the (S) - glycidyl methacrylate by chromatography on silica gel (Merck 60; 40-63 μm) (600 g of silica for 20 g of product deposited; eluent: dichloromethane). Efficiency: 35%

Enantiomeric excess: 99.8% (determined by CGL on a chiral column of the Supelco β dex 225, 30 mx 25 mm type); [α] _D ²⁵ = + 29.3; c = 0.564, CH ₂ CI ₂ IR (film) (cm ^'1 ): 3040, 2961, 1725, 1642, 1270, 1168, 913.

¹ H NMR (200 MHz, CDCI ₃ ) δ (ppm): 1.95 (s, 3H); 2.6-2.7 (m, 1H); 2.8-2.9 (m, 1H); 3.9-4.0 (m, 1H); 4.4-4.5 (m, 1H); 5.52 (s, 1H); 6.18 (s, 1H). ¹³ C NMR (50 MHz, CDCI ₃ ) δ (ppm): 18.3; 44.6; 65.2; 126.2; 135.9; 167.0. EXAMPLE 3

Preparation of the optically active polymer with epoxy functions.

1.5 g of polyvinylpyrrolidone are dissolved at 80 ° C in 100 ml of deionized water, then the volume of the mixture is made up to 150 ml with deionized water. At the same time, 204 mg of azo-bis-isobutyronitrile (AIBN) are dissolved in a mixture formed of 6.13 g of optically pure glycidyl methacrylate and 14.30 g of ethylene glycol dimethacrylate (30% by mass of methacrylate glycidyl - 70% by mass of ethylene glycol dimethacrylate) to which is added a mixture composed of 24.64 g of cyclohexanol and 2.43 g of dodecanol. The aqueous phase containing polyvinylpyrrolidone is placed, under nitrogen, in a double-jacket reactor provided with mechanical stirring and a cryostat. To this aqueous phase are added dropwise the glycidyl methacrylate / ethylene glycol dimethacrylate / AIBN and cyclohexanol / dodecanol mixtures. The reaction medium, stirred at 200 rpm, is heated to 70 ° C for 2 hours then to 80 ° C for 6 hours and finally left at room temperature for 2 hours. The polymer beads are recovered with 95% ethanol. The polymer beads are then divided into three fractions and subjected to stirring using a shaker for 2 hours and the solvent is removed by decantation. Each fraction is then washed with 30 ml of 95% ethanol, stirred using a shaker (2 hours) and the solvent is then removed by decantation. This operation is repeated 4 to 5 times. The polymer beads are then dried in a vacuum oven at 40 ° C for 4 hours. Then they are separated by passing through three sieves: 500 μm, 300 μm and 106 μm. Four fractions are thus obtained. Elementary analysis:

Calculated: C: 60.17%; H: 7.06%; O: 32.77%

Experimental: C: 59.75%; H: 7.40%; O: 32.85%. fo: 2.11 meq. / g. EXAMPLE 4

Synthesis of a modified polymer according to the invention of the polyaminoalcohol type

Under an argon atmosphere, the chiral polymer obtained in Example 3

(1 mmol of epoxide) is suspended in 2 ml of anhydrous dimethylformamide then 3 equivalents of an amine (nucleophilic agent) are added while mechanically stirring (anchor) the reaction medium (180 rpm). The following table summarizes all of the reactions carried out.

Similarly, the modified polymers of Examples 4.7 and 4.8 are prepared by reaction of the following amines with the chiral polymer obtained in Example 3.

EXAMPLE 5 Preparation of Catalyst Complexes from Modified Polymers Prepared in Example 4

The catalyst is prepared in situ. Under an argon atmosphere, one of the polyaminoalcohol type ligands prepared in Example 4 and RuCI ₂ (p-cymene) ₂ are suspended in isopropanol, in a ligand / metal molar ratio of 4/1 , (2 ml for 3.7 mg of RuCI ₂ (p-cymene) ₂ ). This suspension is stirred for 30 minutes at 80 ° C. A color change from yellow to red in the reaction medium and the beads is observed.

The following table summarizes all of the reactions carried out.

EXAMPLE 6 Use of the catalyst complexes prepared in Example 5 in the reduction of acetophenone

After cooling to room temperature one of the catalysts prepared in Example 5, and acetophenone are added so as to obtain a substrate / metal ratio of 20/1. Then a 0.03 mol / l solution of potassium tert-butoxide in isopropanol (Ru / base ratio of 1/5) is added. The reaction mixture is stirred for 3 hours. The determination of the enantiomeric excesses is carried out by CGL on a Supelco type chiral column (β-dex 225 30 mx 25 mm). The results obtained with the various ligands are collated in the following table:

EXAMPLE 7

Preparation of optically pure 3-phenyl-oxiranylmethyl 2-methyl-acrylate.

2 g (13 mmol) of (2R, 3R) - (3-methyl-oxiranyl) -methanol are dissolved in 20 ml of toluene. The reaction medium is magnetically stirred at 0 ° C under argon. 3.75 ml (26.6 mmol) of triethylamine are added, then 1.6 ml (16 mmol) of methacryloyl chloride. The reaction medium is heated to 110 ° C. After 24 hours, the mixture diluted with 30 ml of toluene is washed 3 times with 20 ml of deionized water, then 3 times with 20 ml of a saturated aqueous solution of NaHCOs. The organic phase is dried with MgSO ₄ and the solvent is evaporated. 2.83 g of (2R, 3R) -2-methyl-acrylate of 3-phenyl-oxiranylmethyl are obtained. Efficiency = 97% [α] _D = + 49.6 (c = 1, CH ₂ CI ₂ ); Enantiomeric excess = 99.5%

¹ H NMR (200 MHz, CDCI ₃ ) δ (ppm): 2.00 (s, 1 H), 3.30-3.35 (m, 1 H), 3.85 (d, 1 H; J = 2 Hz), 4.15-4.25 (dd, 1 H; J = 5.80 Hz), 4.55-4.60 (dd, 1 H. J = 3.3 Hz, J = 12.3 Hz), 5.65 (s, 1 H), 6.20 (s, 1 H), 7.30-7.40 (m, 5H)

³ C NMR (50 MHz, CDCI ₃ ) δ (ppm): 18.4; 56.5; 59.4; 64.5; 125.8; 126.4 128.5; 128.6; 135.9; 136.3; 167.0.

EXAMPLE 8 Preparation of an optically active copolymer with epoxy functions.

0.63 g of polyvinylpyrrolidone is dissolved at 80 ° C in 150 ml of deionized water. In parallel, 4 g of 3-phenyl-oxiranylmethyl 2-methyl-acrylate are mixed with 6 g of ethylene glycol dimethacrylate. 1.56 g of dodecanol, 15.27 g of cyclohexanol are added to this mixture, and 82 mg of AIBN. In a double jacket reactor equipped with mechanical stirring and a cryostat, the aqueous phase containing the polyvinylpyrrolidone is introduced under nitrogen. Then the 2-methyl-acrylate mixture of 3-phenyl-oxiranylmethyl / ethylene glycol dimethylacrylate / AIBN / dodecanol / cyclohexanol is introduced dropwise into the reactor. The reaction medium is stirred at 600 rpm, heated at 70 ° C for 2 hours then at 80 ° C for 6 hours, it is cooled to room temperature for 2 hours. The copolymer beads are recovered with 96% ethanol, and divided into three fractions which are stirred using a shaker for 2 hours. The supernatant of each fraction is replaced with 30 ml of 96% ethanol. This operation is repeated 4 to 5 times. The beads are separated using three 80 μm, 50 μm, and 25 μm sieves. Four fractions are thus obtained. Elementary analysis: Calculated C: 65.02%, H: 7.80%, O: 28.18% Experimental C: 62.94%, H: 6.96%, O: 28.88%. fo = 1.83 meq / g EXAMPLE 9

Preparation of an optically active copolymer with epoxy functions.

3 g of polyvinyl alcohol are dissolved at 80 ° C in 150 ml of deionized water. In parallel, 2.6 g of glycidyl methacrylate are mixed with 6 g of 1,4-divinylbenzene (purity: 80%). 1.06 ml of dodecanol, 12.48 ml of cyclohexanol are added to this mixture, as well as 188 mg of AIBN. In a double jacket reactor equipped with mechanical stirring and a cryostat, the aqueous phase containing the polyvinyl alcohol is introduced under nitrogen. Then the glycidyl methacrylate / divinylbenzene / AIBN / dodecanol / cyclohexanol mixture is introduced dropwise into the reactor. The reaction medium is stirred at 400 rpm, heated to 70 ° C for 2 hours then to 80 ° C for 6 hours, then cooled to room temperature for 2 hours. The copolymer beads are recovered with 96% ethanol, and washed with acetone using a soxhlet for 8 hours. The polymer is dried.

Elementary analysis:

Calculated C: 81.87%, H: 7.75%, O: 10.37%

Experimental C: 82.39%, H: 7.98%, O: 9.62% f o = 2.11 meq / g

EXAMPLE 10

Preparation of polymers modified according to the invention of polyaminoalcohol type.

Under an argon atmosphere, the chiral polymer obtained in Example 8 (1 mmol of epoxide) is suspended in a minimum of anhydrous dimethylformamide. 10 equivalents of a nucleophilic amine are added while mechanically agitating the reaction medium (100 rpm). After 24 hours at 100 ° C., the reaction medium is decanted in a flask. The supernatant is replaced with 50 ml of 96% ethanol. The bottle is placed on a shaker for 1 hour, then the supernatant is replaced with 50 ml of deionized water. These alternating washes with ethanol and water are repeated several times before the polymer is dried using a vacuum oven for 4 hours. The following table summarizes all of the reactions carried out starting from three different amines.

EXAMPLE 11 Synthesis of a modified polymer according to the invention of the polyaminoalcohol type.

Under an argon atmosphere, the chiral polymer obtained in Example 9 (1 mmol of epoxide) is suspended in benzylamine while mechanically stirring the reaction medium (100 rpm). After 24 hours at 80 ° C, the reaction medium is centrifuged at 4000 rpm. The supernatant is removed to be replaced with 96% ethanol. Then the polymer is dried using a vacuum oven for 4 hours.

EXAMPLE 12

Preparation of catalyst complexes from modified polymers prepared in Examples 10 and 11.

The catalyst is prepared in situ. Under an argon atmosphere, one of the polyaminoalcohol ligands prepared in Example 10 or 11 and [RuCI ₂ (p-cymene)] ₂ are suspended in isopropanol, in a ligand / metal molar ratio of 4/1, (2ml for 3.7 mg of [RuCI ₂ (p-cymene)] ₂ ) _. . This suspension is stirred for 1 hour at 80 ° C. A color change from yellow to red in the reaction medium is observed.

The following table summarizes all of the reactions carried out.

EXAMPLE 13 Use of the catalyst complexes prepared in Example 12 in the reduction of acetophenone.

At room temperature, one of the catalysts prepared in Example 12 and acetophenone are added (substrate / metal molar ratio: 20/1). Then a 0.03 mol / l solution of potassium tert-butoxide in isopropanol (Ru / base ratio: 1/5) is added. The reaction mixture is stirred magnetically. Samples are taken over time and analyzed. The enantiomeric excesses are determined by CPG on a Supelco type chiral column (Lipodex A 30x25). The results with the different ligands are collated in the following table:

EXAMPLE 14

Preparation of an optically active copolymer with epoxy functions 0.73 g of polyvinylpyrrolidone are dissolved at 80 ° C. in 150 ml of deionized water.

In parallel, 7 g of glycidyl methacrylate are mixed with 3 g of ethylene glycol dimethacrylate, 1.18 g of dodecanol, 12.06 g of cyclohexanol are added to this mixture, and 105 mg of AIBN. In a double jacket reactor equipped with mechanical stirring and a cryostat, the aqueous phase containing the polyvinylpyrrolidone is introduced under nitrogen. Then the mixture of glycidyl methacrylate / ethylene glycol dimethacrylate / AIBN / dodecanol / cyclohexanol is introduced dropwise into the reactor. The reaction medium is stirred at 400 rpm, heated at 70 ° C for 2 hours then at 80 ° C for 6 hours, it is cooled to room temperature for 2 hours. The copolymer beads are recovered with 96% ethanol, and divided into three fractions which are stirred using a shaker for 2 hours. The supernatant of each fraction is replaced with 30 ml of 96% ethanol. This operation is repeated 4 to 5 times. The beads are separated using three 80 μm, 50 μm and 25 μm sieves. Four fractions are thus obtained. Food analysis: - Calculated C: 59.50%, H: 7.19% O: 33.25%

- Experimental C: 59.86%, H: 7.28%, O: 32.85%

- fo = 4.90 meq / g

EXAMPLE 15 Synthesis of a modified polymer according to the invention of the polyaminoalcohol type.

Under an argon atmosphere, the chiral polymer obtained in Example 14 (1 mmol of epoxide) is suspended in benzylamine while mechanically stirring the reaction medium (100 rpm). After 24 hours at 80 ° C., the reaction medium is decanted in a flask. The supernatant is replaced with 50 ml of 96% ethanol. The bottle is placed on a shaker for 1 hour, then the supernatant is replaced with 50 ml of deionized water. These alternating washes with ethanol and water are repeated several times before the polymer is dried using a vacuum oven at 50 ° C for 4 hours.

EXAMPLE 16

Preparation of catalyst complexes from modified polymers prepared in Example 15.

The catalyst is prepared in situ. Under an argon atmosphere, the polyaminoalcohol type ligand prepared in Example 15 and [RuCl ₂ (p-cymene)] 2 are suspended in isopropanol, in a ligand / metal molar ratio of 4/1, ( 2 ml for 3.7 mg of [RuCl ₂ (p-cymene)] _2. This suspension is stirred for 1 hour at 80 ° C. A color change from yellow to red in the reaction medium is observed.

EXAMPLE 17

Use of the catalyst complexes prepared in Example 16 in the reduction of acetophenone.

At room temperature, the catalyst prepared in Example 16 and acetophenone are added (substrate / metal molar ratio: 20/1). Then a 0.03 mol / l solution of potassium tert-butoxide in isopropanol (Ru / base ratio: 1/5) is added. The reaction mixture is stirred magnetically. Samples are taken over time and analyzed. The enantiomeric excesses are determined by CPG on a Supelco type chiral column (Lipodex A 30x25). The results obtained are collated in the following table:

Claims

1 - Optically active polymer which can be obtained by radical or anionic polymerization of an optically active ethylenic monomer with an epoxide function carrying at least one chiral center optionally in the presence of one or more other copolymerizable ethylenic monomers, said reaction being carried out in conditions which do not cause the opening of the epoxy functions.

2 - Polymer according to claim 1 obtainable by copolymerization of an optically active ethylenic monomer with epoxy function carrying at least one chiral center with a copolymerizable ethylenic monomer.

3 - Polymer according to claim 2, characterized in that the molar ratio of the desired fraction of the optically active ethylenic monomer with epoxide functions to the fraction derived from the copolymerizable ethylenic monomer varies from 1-100: 0-99.

4 - Polymer according to one of claims 1 to 3, characterized in that each ethylenic monomer comprises a carbonyl, ester, nitrile, amide or alpha ether function of the ethylenic double bond.

5 - Polymer according to any one of claims 1 to 4, characterized in that each ethylenic copolymerizable monomer comprises at least two ethylenic double bonds each having a carbonyl, ester, nitrile, amide or ether group in alpha of the double bond.

6 - Polymer according to any one of claims 1 to 5, characterized in that it is composed of two types of recurring units A and B of formula: the motif A carrying at least one optically active chiral center at the epoxide function; in which :

- * indicates the possible location of a carbon of stereochemistry R or S well determined;

- n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4;

- X, Y ¹ and Y ² are independently chosen from -O-, -S- and -NT- where T represents a hydrogen atom, an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- B represents a divalent radical chosen from alkylene; cycloalkylene; alkylene interrupted by one or more arylene and / or cycloalkylene groups; or arylene; each of the alkylene, cycloalkylene or arylene groups being optionally substituted; - R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are independently chosen from a hydrogen atom, a alkyl, cycloalkyl or aryl group, said group being optionally substituted;

R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² independently represent optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkylcarbonyloxy or optionally substituted arylcarbonyloxy; it being understood that R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ¹¹ and R ¹² can also represent 1-alkenyl, and R ⁷ , R ⁸ and R ⁹ can also represent a polysiloxyl group.

7 - Polymer according to claim 6, characterized in that X, Y ¹ and Y ² represent an oxygen atom and B represents optionally substituted alkylene.

8- Polymer according to any one of claims 6 to 7, characterized in that R ° and R ³ independently represent a hydrogen atom, an optionally substituted aryl group; or an optionally substituted alkyl group; R ⁴ represents optionally substituted alkyl or an optionally substituted aryl group; and R ¹ and R ² are independently selected from a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted aryl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group.

9- Polymer according to any one of claims 6 to 8, characterized in that R ⁹ and R ¹⁰ are independently chosen from optionally substituted alkyl and an optionally substituted aryl group; R ⁷ , R ⁸ , R ¹¹ and R ¹² independently represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group.

10- Polymer according to any one of claims 6 to 9, characterized in that R °, R ¹ , R ² , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ¹¹ and R ¹² represent a hydrogen atom ; R ⁴ , R ⁹ , R ¹⁰ represent a methyl group; and R ³ represents H, methyl or phenyl. 11- Polymer according to claim 10 wherein X, Y ¹ , and Y ² represent an oxygen atom and B represents ethylene.

12- Polymer according to any one of claims 1 to 4 characterized in that the ethylenic monomer with epoxide function comprises a carbonyl, ester or amide function in alpha of the ethylenic double bond, and in that the ethylenic copolymerizable monomer comprises at least two ethylenic double bonds.

13- Polymer according to any one of claims 1 to 4 and 12, characterized in that it is composed of two types of recurring patterns A_and Ç_ of formulas:

the motif A carrying at least one optically active chiral center at the epoxide function; in which :

- * indicates the possible location of a carbon of stereochemistry R or S well determined;

- n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4;

- X is chosen from -O-, -S- and -NT- where T represents a hydrogen atom, an alkyl, cycloalkyl or aryl group, said group being optionally substituted; - E is chosen from alkylene optionally substituted and optionally interrupted by one or more divalent groups - Si (A) (B) - where A and B are independently chosen from optionally substituted alkyl or optionally substituted aryl; the divalent group of formula -Ch ¹ -Ar ° -Ch ² - where Ch ¹ , Ch ² independently represent a bond, an oxygen atom, a sulfur atom or -NT-, T being as defined above, and, Ar ° represents optionally substituted arylene; a relationship ; an oxygen atom; the divalent group -NT- in which T represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group; or a chain -Ar'-X ^ alk-X ^ Ar ² - where Ar ¹ and Ar ² are independently chosen from optionally substituted arylene, alk represents optionally substituted alkylene and X ¹ , X ² independently represent O or -NT ° -, T ° being as defined above for T;

- R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are independently chosen from a hydrogen atom, a alkyl, cycloalkyl or aryl group, said group being optionally substituted;

R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , and R ¹⁸ , may also represent optionally substituted alkoxy; optionally substituted aryloxy; optionally substituted alkylcarbonyloxy; optionally substituted arylcarbonyloxy; or a polysiloxyl group. it being understood that R ⁵ , R ⁶ , R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ may also represent 1-alkenyl, and R ¹³ , R ¹⁴ and R ¹⁵ may also represent a polysiloxyl group.

14- Polymer according to claim 13 characterized in that X represents an oxygen atom.

15- Polymer according to any one of claims 13 to 14 characterized in that R ° and R ³ independently represent a hydrogen atom, an optionally substituted aryl group, an optionally substituted alkyl group; R ⁴ represents optionally substituted alkyl or an optionally substituted aryl group; and R ¹ and R ² are independently selected from a hydrogen atom, an optionally substituted alkyl group, and an optionally substituted aryl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group.

16- Polymer according to any one of claims 13 to 15, characterized in that R °, R ¹ , R ² , R ⁵ , R ⁶ , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ represent a hydrogen atom; E represents phenylene; n is 1; X represents an oxygen atom; R ⁴ represents methyl and R ³ represents a hydrogen atom or a phenyl group.

17- Process for the preparation of a polymer according to any one of claims 1 to 16, characterized in that an optically active monomer having an epoxy function carrying at least one chiral center is polymerized by radical means in the presence of one or more other copolymerizable ethylenic monomers, this polymerization being carried out in the presence of a radical initiator.

18- The method of claim 17, characterized in that the radical initiator is azobisisobutyronitrile or benzoyl peroxide.

19- Method according to any one of claims 17 and 18 characterized in that the epoxide-functional monomer has the formula I:

in which - * indicates the possible location of a carbon of well-defined R or S stereochemistry; - n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4; - X represents -O-, -S- or -NT- where T represents a hydrogen atom; an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independently chosen from a hydrogen atom; an alkyl, cycloalkyl, aryl, alkoxy, alkylcarbonyloxy or arylcarbonyloxy group, said group being optionally substituted; it being understood that R ⁵ and R ⁶ may also represent 1-alkenyl; with a copolymerizable monomer of formula II:

in which :

- Y ¹ , Y ² represents -O-, -S- or -NT- where T represents a hydrogen atom, an alkyl, cycloalkyl or aryl group, said group being optionally substituted; - B represents alkylene, cycloalkylene, arylene or alkylene interrupted by one or more arylene and / or cycloalkylene; each alkylene, cycloalkylene or arylene being optionally substituted;

- R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are independently chosen from a hydrogen atom, an alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyloxy or arylcarbonyloxy group, said group being optionally substituted; it being understood that R ⁷ , R ⁸ , R ¹¹ and R ¹² can also represent 1-alkenyl, and R ⁷ , R ⁸ and R ⁹ can also represent a polysiloxyl group. 20- Process according to claim 19, characterized in that the formula I, X represents O and in the formula II, Y ¹ and Y ² both represent an oxygen atom and B represents optionally substituted alkylene or an optionally substituted arylene group or an optionally substituted arylene group.

21- A method according to any one of claims 19 and 20, characterized in that in formula I, R ° and R ³ independently represent a hydrogen atom, an optionally substituted aryl group, or an optionally substituted alkyl group; R ⁴ represents optionally substituted alkyl or an optionally substituted aryl group, and R ¹ and R ² independently represent a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted aryl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group.

22- Method according to any one of claims 19 to 21, characterized in that in formula II, R ⁹ and R ¹⁰ are independently chosen from substituted alkyl and an optionally substituted aryl group; and R ⁷ , R ⁸ , R ¹¹ and R ¹² independently represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group.

23- Method according to any one of claims 19 to 22, characterized in that in formula I, R °, R ¹ , R ² , R ⁵ and R ⁶ represent a hydrogen atom; R ⁴ represents optionally substituted alkyl and, in formula II, R ⁷ , R ⁸ , R ¹¹ , R ¹² are hydrogen atoms and R ⁹ , and R ¹⁰ represent a methyl group; and R ³ represents H, a methyl group or a phenyl group.

24- A method according to claim 14 characterized in that Ro, Ri, R2, R5, Re, R ₇ , _δ , R1 ₁ and R ₁₂ represent a hydrogen atom; R ₄ , R ₉ and R ₁₀ represent a methyl group; and X, Y ¹ and Y ² represent an oxygen atom.

25- Method according to any one of claims 17 and 18 characterized in that the epoxide-functional monomer has the formula I:

- * indicates the possible location of a carbon of stereochemistry R or S well determined;

- n is an integer between 1 and 10, preferably chosen from 1, 2, 3 and 4;

- X represents -O-, -S- or -NT- where T represents a hydrogen atom; an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- R °, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independently chosen from a hydrogen atom; an alkyl, cycloalkyl or aryl group, said group being optionally substituted;

- it being understood that R ⁵ and R ⁶ may also represent 1-alkenyl; with a copolymerizable monomer of formula III:

in which

- E is chosen from alkylene optionally substituted and optionally interrupted by one or more divalent groups - Si (A) (B) - where A and B are independently chosen from optionally substituted alkyl or optionally substituted aryl; the divalent group of formula -Ch ¹ -Ar ° -Ch ² - where Ch ¹ , Ch ² independently represent a bond, an oxygen atom, an atom sulfur or -NT-, T being as defined above, and Ar ° represents optionally substituted arylene; a relationship ; an oxygen atom; the divalent group -NT- in which T represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group; or a chain -A ^ -X ^ alk-X ^ Ar ² - where Ar ¹ and Ar ² are independently chosen from optionally substituted arylene, alk represents optionally substituted alkylene and X ¹ , X ² independently represent O or -NT ° -, T ° being as defined above for T;

- R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are independently chosen from a hydrogen atom, an alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyloxy or arylcarbonyloxy group, said group being optionally substituted; it being understood that R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ may also represent 1-alkenyl, and R ¹³ , R ¹⁴ , R ¹⁵ may also represent a polysiloxyl group.

26- A method according to claim 25 characterized in that in formula I, X represents an oxygen atom.

27- A method according to any one of claims 25 and 26 characterized in that in formula I, R ° and R ³ independently represent a hydrogen atom, an optionally substituted aryl group, or an optionally substituted alkyl group, R ⁴ represents optionally substituted alkyl or an optionally substituted aryl group, and R ¹ and R ² independently represent a hydrogen atom or an optionally substituted alkyl group; and R ⁵ and R ⁶ are independently chosen from a hydrogen atom, an optionally substituted alkyl group and an optionally substituted aryl group.

28- A method according to any one of claims 25 to 27 characterized in that in formula III, R ¹⁵ and R ¹⁶ are independently selected from optionally substituted alkyl, optionally substituted aryl and a hydrogen atom; and R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ independently represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group. 29- A method according to any one of claims 25 to 28 characterized in that in formula I, R °, R ¹ , R ² , R ⁵ and R ⁶ represent a hydrogen atom; R ⁴ represents optionally substituted alkyl, and R ³ represents H or phenyl, and, in formula III, R ¹³ , R ¹⁴ , R ¹⁷ and R ¹⁸ are hydrogen atoms; R ¹⁵ and R ¹⁶ represent a methyl group, a phenyl group or a hydrogen atom.

30- A method according to any one of claims 25 to 29 characterized in that the compound of formula I is glycidyl methacrylate and the compound of formula III is a divinylbenzene.

31- Method according to any one of claims 17 to 30, characterized in that the polymerization is carried out in a two-phase medium comprising water, an organic solvent and a very hydrophilic polar compound chosen from polyvinylpyrrolidone; polyvinyl alcohols and their ethers; polyvinylacetates; polyvinylacetamides; gelatin; methylcellulose; polymethacrylamide; salts of polymethacrylic acid; polymethacrylic acid; alkaline earth metal phosphates; and the polymers resulting from the polymerization of one of the following ethylenically double-bonded monomers:

where R _x and R _y independently represent a hydrocarbon chain, it being understood that at least one of R _x or R _y is a fatty hydrocarbon chain having from 8 to 24 carbon atoms;

where Rz is as defined above for Rx and has from 8 to 24 carbon atoms;

CH ₂ = Ç— CONH (CH ₂ ) ₁₀ CONHCH ₂ CH ₂ Sθ ₃ -Na ⁺ CH-

32- A method according to claim 31, characterized in that said organic solvent is chosen from optionally substituted aromatic hydrocarbons; halogenated or non-halogenated aliphatic hydrocarbons; ketones; amides; esters; pyridine; propylene carbonate; cyclic ethers; C ₄ -Ca cycloalkanols; CiC-iβ alkanols; and their mixtures.

33- A method according to claim 31 or claim 32, characterized in that the two-phase medium further comprises pore-forming solvents chosen from Cs-Cs cycloalkyl alcohol and C-i-C-is alkanol.

34- Method according to claim 33, characterized in that the two-phase medium comprises, as pore-forming solvents, a mixture of cyclohexanol and dodecanol or a mixture of cyclohexanol and lauryl alcohol. 35- A method according to any one of claims 17 to 30 characterized in that the polymerization is carried out anionically in the presence of a stabilizer of the active center of the polymerization chosen from tertiary alcoholates of alkali metals; alkali metal halides; alkyd polydentate alcoholates; and aluminum alkyls.

36- A method according to claim 35 characterized in that the stabilizer is chosen from lithium chloride; lithium tert-butoxide; and lithium 3-methyl-3-pentylate, the preferred stabilizer being lithium chloride.

37- A method according to any one of claims 35 and 36 characterized in that the polymerization is carried out in the presence of a polymerization initiator chosen from alkyllithium; enolates of alkali metal esters; and primary and secondary alkali metal alcoholates.

38- A method according to claim 37 characterized in that the polymerization initiator is chosen from sec-butyllithium; 1,1-diphenyl-3-methylpentyllithium; and 1, 1, 4,4-tetraphenyl-1, 4-dilithiobutane.

39- A method according to any one of claims 35 to 38 characterized in that the polymerization is carried out in a solvent chosen from aliphatic, cyclic or aromatic hydrocarbons; ethers; pyridine and their mixtures.

40- Method according to any one of claims 35 to 39 characterized in that the polymerization is carried out at a temperature between -100 ° C and 0 ° C, preferably between -60 and -30 ° C

41- Optically active polymer which can be obtained by stereoselective regiospecific reaction of a nucleophilic agent on a polymer as defined in any one of claims 1 to 16, whereby the partial or total regiospecific stereoselective opening of the functions is brought about epoxides of said reactive polymer. 42- Polymer according to claim 41, characterized in that said nucleophilic agent comprises, as nucleophilic site, a halogen atom, a carbon atom, an oxygen atom, a sulfur atom, a nitrogen atom, a phosphorus atom or a selenium atom.

43- Polymer according to claim 42, characterized in that said nucleophilic agent is an amine, a guanidine, a morpholine or a hydroxylamine.

44- Use of a polymer according to any one of claims 1 to 16 as a polymeric material for the immobilization of enzymes.

45- Use of a polymer according to any one of claims 41 to 43 as a polymer matrix usable in chiral chromatography.

46- Use of a polymer according to any one of claims 41 to 43 as a polymeric support usable in synthesis on solid phase.

47- Use of a polymer according to any one of claims 41 to 43 as a ligand optionally after transformation into oxazaborolidine or phosphoramidate in the preparation of transition metal complexes or as a chiral inducer, in stereoselective catalysis.

48- Use according to claim 47 to catalyze the stereoselective reduction of carbonyl and imine functions or to catalyze reactions involving the formation of C-C bonds.

49- polymer material usable as stationary phase in chiral chromatography, obtainable by grafting reaction of a polymer according to any one of claims 41 to 43 on a support conventionally used in chromatography. 50- Use of a polymeric material according to claim 49 in chiral chromotography.

51- Metallic complex of a transition metal comprising a polymer according to any one of claims 1 to 16 or 41 to 43 as a ligand.

52- Complex according to claims 51 characterized in that the transition metal is ruthenium, iridium or rhodium, preferably ruthenium.