EP1631539A1 - Esters of allyl substituted by a difluoromethylene group, method for the synthesis thereof and use thereof - Google Patents

Abstract

The invention relates to a compound of formula (I) wherein Rf is a radical carrying a perfluoromethylene group wherein said group ensures a link with the rest of the molecule; R1 and R3, which can be the same or different, are selected from hydrogen and alkyl or aryl radicals; Γ is an electro-attracting group such that Γ-O-H is an acid whose pKa (in water) is at the most equal to 8, advantageously to 6, preferably 5. Said compounds are used for the synthesis of nitrogenous heterocycles.

Description

 SUBSTITUTED ALLYL ESTERS

BY A DIFLUOROMETHYLENE GROUP,

THEIR SYNTHESIS PROCESS AND THEIR USE

The subject of the present invention is compounds forming an allyl ester substituted with a difluoromethylene group.

It also relates to a synthesis route of these compounds as well as their use in cycloaddtion processes, in particular 3 + 2 cycloadditions.

Over the past decade, compounds carrying fluoroalkyl groups have grown considerably, particularly in agrochemicals and pharmaceuticals.

In particular, heterocycles, in particular nitrogen-containing and in particular 5-membered, have become relatively frequent when they carry groups (-CF ₂ ). However, the synthesis of such compounds is difficult and often requires a high sequence of steps.

Also, one of the aims of the present invention is to provide a family of precursors for these nitrogen heterocycles. The use of these precursors should be easy, should not require many steps.

Another object of the present invention is to provide a process for the synthesis of said precursors.

Another object of the present invention is to provide a technique for using these precursors.

These aims, and others which will appear subsequently, are achieved by means of compounds of formula (I):

in which :

^» > R _f is a radical carrying a perfluoromethylene group which group ensures the bond with the rest of the molecule: *> R ₁ and R _3> which may be the same or different, are chosen from hydrogen and the radicals alcohols or aryls; Ψ is an electron-withdrawing group such that Ψ-OH is an acid whose pKa (in water) is at most equal to 8, advantageously 6, preferably 5.

According to the present invention, it is desirable that the Ψ-OH group constitutes an acid whose pKa is at least equal to 1, advantageously to 2. In fact, it is desirable that the Ψ-O ^"group does not constitute a good group therefore, both for use as a precursor of cycloaddition and for its synthesis.

It is desirable that R, and R ₃ do not clutter the molecule too much, so it is advisable to avoid that Ri and / or R ₃ are attached to the double bond by a tertiary or even secondary carbon.

Thus, it is preferable that at least one of Ri and R ₃ is a light alkyl (light, that is to say at most 4 carbons) or better still, hydrogen.

Thus, it is preferred that R is hydrogen; it is also preferred that R ₃ is hydrogen; and it is even more preferred that R 1 and R ₃ are hydrogen.

Advantageously R _f is of formula (II)

GEA - (CX ₂ ) _P - where:

- The X, similar (that is to say that they are identical) or different, represent a chlorine, a fluorine or a radical of formula C _n F _{2n +} ι with n integer at most equal to 5, preferably to 2, with the condition that the Xs of the methylene group carrying the open bond are not chlorine and that at least one of them is a fluorine atom, advantageously the Xs of methylene carrying the open bond are either fluorine atoms or else a fluorine atom and a radical of formula C _n F _{2n +} ι (such radicals are indeed considered to be electronically close to fluorine atoms),

- GEA is a hydrocarbon or electro-attractor group (that is to say that the Hammett constant σ _p (sigma p) is> 0, advantageously at least equal à, 0,2), preferably inert, advantageously, when p is equal to 1, an electron-withdrawing group (cf. preceding lines); - p is a positive integer, that is, it cannot understand the value 0.

GEA is advantageously fluorine especially when p is less than or equal to 2.

The X's are advantageously all fluors, especially when p is less than or equal to 2.

Another value of GEA (electron-withdrawing group) is the chlorine value; in this case, GEA is chlorine.

p represents an integer advantageously at most equal to 4, preferably to 2;

GEA advantageously represents an electron-withdrawing group the possible functions of which are inert under the conditions of the reaction, advantageously fluorine or a perfluorinated residue of formula C _n F _{2n +} ι, with n integer at most equal to 8, advantageously 5,

The total number of carbons of R _f is advantageously between 1 and 15, preferably between 1 and 10.

It is interesting that R _f has the formula C _r F _{2r + 1} with r positive integer ranging from 1 to 10, advantageously from 1 to 5, preferably from 1 to 3.

The present invention is particularly advantageous for Rf of low molecular weight, that is to say those which are relatively volatile (that is to say corresponding to an R _f H whose boiling point under atmospheric pressure is at most equal to 100 ° C). The technique is particularly interesting for Rf having a radical having an odd number of carbons and a particular mention must be made for the Rf in Ci, C ₂ and C ₃ . Thus the trifluoromethyl, pentafluoroethyl and heptafluoropropyl radicals are among the preferred values of R _f .

According to the present invention, it is preferable that Ψ represents an acyl, advantageously such that the pKa (measured or reduced to a value in water) is at least equal to approximately 2 (the expression approximately is used here to underline that the number which follows corresponds to a mathematical rounding), advantageously to around 3.

Usually Ψ-OH is an alkanoic acid, advantageously from 1 to 8 carbon atoms, preferably from 2 to 5. Economically, the value of Ψ equal to acetyl is the most interesting.

As mentioned above, another object of the present invention is to provide an easy access route to the molecules mentioned above.

This object is achieved by means of a process for synthesizing the compound of formula (I), which involves bringing d d) into contact:

(Where Ξ (xi) represents a halogen leaving group (heavier than fluorine, chlorine or bromine) or pseudohalogen such that ΞH has a Hammett constant at least equal to that of trifluoroacetic acid, advantageously at least equal to that mesylic acid) with a base chosen from strong nitrogenous bases whose associated acid has a pKa at least equal to 12 among anionic bases with the condition that when the base is a non-nitrogenous anionic base the latter is present of a solvent or a mixture of polar solvents.

To date, access to the compounds of formula (I) has not been described; a good reason for this, is that the most direct route from known compounds is difficult is difficult and, in general, leads to products other than the desired one (see in particular the comparative examples).

The compounds of formula (III) are fragile compounds whose purification is often difficult, or almost impossible, due to the instability, in particular thermal, of the compounds of formula (III), especially when Ξ represents a halogen forming a good group leaving as bromine or iodine.

The chlorine derivative is a little more stable.

The technique for synthesizing the compounds of formula (III) has been described in international PCT application WO 01/58833, filed in the name of the Applicant.

In general, the synthesis of the compounds of formula (III) can be carried out by the reaction defined by the equation below:

with Z representing a methylene group (optionally substituted but preferably unsubstituted) carrying Ψ-O- and Ξ limited here to Cl and Br, or even I (but the sulfonyl iodide is not stable; its existence which could not be transient, has not been demonstrated and cannot be implemented, except to do so in situ).

The tearing of the HΞ acid from the molecule of formula (III) to give the molecule of formula (I) is difficult to control, most of the bases giving nucleophilic substitution or degradation or even elimination reactions. a halogen from the Rf group.

Following the study which led to the present invention, it has been shown that by choosing certain bases, the reaction could take place in the desired direction. It has also been shown that other bases could be used provided that the operating conditions, and in particular the reaction medium, are chosen.

It can thus be indicated that the following bases can give good results: - non-anionic bases in which a nitrogen doublet is conjugated with a carbon-nitrogen double bond; these bases can be used, either alone in stoichiometric or over-stoichiometric quantities, or can be used in quantitative quantities with another base, preferably more basic than these said non-anionic bases; in particular these bases can be used with the bases below, which they are in principle used in stoichiometric or super-stoichiometric amounts; - Anionic nitrogen bases which give good results, but are generally expensive, and the effect of which is all the better when polar aprotic solvents are used as solvents; - non-nitrogenous anionic bases, advantageously not derived from an alcohol or water (hydroxide ions and alcoholates are respectively to be avoided and preferably to be avoided). These bases give good results only when a polar solvent is used, the donor index of which is at least equal to 10, advantageously 15, preferably 20. When the polar solvents are used according to the process of the invention, it is preferable that these polar solvents have a dielectric constant ε (epsilon) at least equal to 7. Furthermore, when the solvent is basic, that is to say say when it has a high donor number (greater than 20), it is preferable that this basicity is relatively low in the sense of the basicity of Bronsted, that is to say that the pKa of the associated acid of said solvent is greater than 5, advantageously 6, more preferably 7.

Advantageously, said reaction medium is aprotic and anhydrous. In particular, it is desirable that this aprotic and anhydrous medium is such that the strongest acid present in the medium, without taking into account the substrate, has a pKa at least equal to 20, better to 25, advantageously to 30, preferably 35. This constraint aims to avoid parasitic reactions during the tearing of the proton from the substrate by the base; in fact the anions resulting from the tearing of a proton by a base are nucleophiles which can lead to a nucleophilic substitution reaction which is not desired.

Thus it is preferable that such anions are not formed. More generally, it is preferable that the constituents of the reaction mixture are not, in contact with the base used, capable of giving nucleophyte anions. Strong acids (pKa ≤ 2), or even medium acids (2 <pKa≤ 4.5) do not, strictly speaking, interfere with the reaction because they consume base, giving only anions with little or no nucleophilicity, and therefore little or no parasitic reaction (s). The acids associated with the bases according to the present invention, or resulting from them, obviously do not harm the present invention. This is the reason why the hydroxide ions, or even alcoholates, are not suitable for the processes according to the present invention. Indeed, they lead to molecules which are to be avoided as solvents.

Thus, it is preferable that, in the reagent, the content of labile hydrogen atoms (that is to say those not corresponding to the pKa specified above) is at most equal to 1/3, advantageously 1 / 4, preferably at 10% (in moles), relative to the initial content in that of said base or of said compound of formula (III) which is not in excess.

One of the advantages of encryptors is that it makes it possible to at least partially overcome solvents with a high donor index.

For the definition of the donor index (or donor number: "donor number") one can refer to the work by Christian Reichardt, Solvents and solvents effects in organic chemistr, p. 19 (1988), a work in which the negative of enthalpy ² (-ΔH expressed in kilocaloriemol) of the interaction between the solvent and antimony pentachloride in a dilute solution of dichloroethane is found as a definition.

In the case of mixtures of solvents, or of solvents containing encryptants, the donor index will be calculated by donor function by multiplying the donor index of each of the solvents by the molar fraction which it represents and by summing these products .

Among the anionic nitrogen bases, mention should be made of the salts, in particular alkali or noteworthy alkali, of amines, silylated or not, as well as silylamines. Among the salts giving the best results, mention should be made of the salified disilylamines and in particular the salts, in particular alkali or alkaline earth, of hexamethyldisilazane (HMDZ).

Among the non-nitrogenous anionic bases, mention should be made of non-oxygenated bases such as, for example, alkali or alkaline earth hydrides, and alkane salts such as butyllithium and alkali carbonates. It should be remembered that the bases of this family must be used in the presence of polar solvents.

Recall that it is desirable to use easily distillable solvents (Eb less than or equal to 120 ° C) and / or miscible with water, advantageously in any proportion in order to more easily treat the reaction mixture.

The bases giving the best results are the bases comprising 2 nitrogen atoms conjugated as already mentioned and as detailed below.

According to an advantageous mode of implementation according to the present invention, said base is nitrogenous and not anionic and corresponds to formula (IV): ° - -A-R2

- where A is a metalloid atom in column VB (column of nitrogen, and advantageously the latter) (the periodic classification of the elements used in this application is that of the supplement to the Bulletin of the Société Chimique de France, January 1966, n ° 1). - where A "is a carbon atom carrying hydrogen or substituted by a hydrocarbon radical R ₅ ,

- where the radical D is:

=> or a metalloid carrying a doublet chosen paimi: the chalcogens advantageously monosubstituted by a monovalent radical R ₆ (in which case the chalcogens constitute said metalloid carrying a doublet),

the metalloids of column VB, in particular nitrogen or phosphorus (in which case the metalloids of column V constitute said metalloid carrying a doublet), preferably nitrogen, which metalloids of column VB are advantageously disubstituted by two monovalent hydrocarbon radicals R ₆ , and R ' ₆ to form a radical D of formula -A' (R ₆ ,) (R ' ₆ ); = or else a radical carrying both a metalloid atom and at least one unsaturation, said one or more unsaturations ensuring the conjugation between a doublet of said metalloid atom and the double bond -A3 = A-; this group is linked to the rest of the molecule by a single bond carried by an atom chosen from sp ² hybridization carbon atoms substituted by a function or a divalent radical R ₇ carrying a hydrogen or optionally substituted by a carbon radical R ₆ .

It should be recalled that in this formula the metalloids of column VB are preferably nitrogen, whether for A "or for A ¹ .

When A "is an atom of column VB, and in particular a nitrogen, it is preferred that D is chosen from those described above and whose single bond ensuring the link with the rest of the molecule is carried by an atom chosen from sp ² hybridization carbon atoms substituted by a function or by a bivalent radical R ₇ carrying a hydrogen or optionally substituted by a carbon radical R ₆ to give a formula of D specified below:

When said carbon carries a hydrogen, this hydrogen is in place of R ₆ so as to give R ₆ the hydrogen value.

As has been said previously, it is desirable that the base of formula (IV) comprises a metalloid atom (saturated, that is to say not carrying a double bond), having a resonance (or conjugation) with a bond π connecting two atoms, at least one of which is a disubstituted and positively charged atom from the column VB; advantageously an organic base comprising a trivalent atom from column VB (column of nitrogen in Mendeleev's table), advantageously nitrogen, an atom whose doublet is directly or indirectly conjugated to a π bond connecting two atoms, including minus one is an atom from column VB (i.e. A). According to a particularly advantageous implementation of the present invention, said π bond connecting two atoms is the π bond of an imine function (> C = N-).

This imine function can be written as follows:

D \ A "= N— R2

R5 - with A "representing a carbon, - with D chosen from: - monosubstituted chalcogens by a monovalent radical R ₆ ,

^• a metalloid of column VB, nitrogen advantageously substituted by two monovalent radicals R and R ′ _{6 in} particular or phosphorus, preferably nitrogen; and

^• those described above where the link with the rest of the molecule is ensured by a bond carried by sp ² carbon atoms substituted by a function or a divalent radical R ₇ carrying a hydrogen or optionally substituted by a carbon radical Ffe.

The radical R is chosen from hydrogen, the values of D and from hydrocarbon radicals, advantageously aryls and especially alkyls.

It is preferable that the radical D and this imine function are arranged in such a way that the atoms of nitrogen and of said metalloid are as far apart as possible, in other words and for example, that the nitrogen of the imine function is that of the two atoms linked by the π bond which is the farthest from the trivalent atom of column V. What has just been said about the imine function is general for all the atoms of column VB linked by the bond π in the case where the bond π has a carbon atom and an atom from column V.

According to the present invention, it is preferred that the organic cation comprising a trivalent atom from the column VB whose doublet is conjugated to a π bond, has a sequence, or rather a skeleton, of formula> N- [C = C] _v -C = r> T <:, with v equal to zero or an integer chosen from the closed interval (that is to say including the limits) 1 to 4, advantageously from 1 to 3, preferably from 1 to 2. Preferably the previous sequence corresponds to the formula:

QC (R ₈ ) = C (R ₆ ) -C (R ₅ ) --- ZN (R ₂ ) with Q representative

- a chalcogen substituted by an aliphatic or aromatic radical R ₉ ; or

^• a disubstituted phosphorus or more preferably a nitrogen disubstituted by two radicals, identical or different, aliphatic or aromatic Rg and R ₁₀ : (Rιo) (R9) N-; with v equal to zero or an integer chosen from the closed interval (that is to say comprising the limits) 1 to 4, advantageously from 1 to 3, preferably from 1 to 2 and where, R ₂ is chosen from hydrocarbon derivatives, advantageously alkyls of at most 4 carbon atoms and hydrogen.

Advantageously, according to the present invention, said trivalent atom of the VB column forms or constitutes a tertiary amine.

More specifically, it is desirable that said organic base comprising a trivalent atom from column VB, the doublet of which is conjugated to a π bond, constitutes a molecule of the following formula:

(Rιo) (Rβ) N- [C (Rβ) = C (Rβ)] vC (Rβ) = N- (R ₂ ) with v equal to zero or an integer chosen from the closed interval (i.e. - say comprising the limits) 1 to 4, advantageously from 1 to 3, preferably from 1 to 2 and where R ₂ , R ₅ , R ₆ and R ₈ , identical or different, are chosen from hydrocarbon groups, advantageously alkyls d '' at most 4 carbon atoms and hydrogen and where R ₁₀ and R ₉ , identical or different, are chosen from hydrocarbon groups, advantageously alkyl groups of at most 4 carbon atoms, one or two of the substituents, R ₂ , R5. Re, Rβ. R9 and R ₁₀ can be linked to other (s) substituents) remaining to form one, two or more rings, in particular aromatic, see below.

The potentiation effect of the base is particularly marked when said π bond connecting two atoms is intracyclic (or a mesomeric form is intracyclic), even when it is intracyclic in an aromatic cycle.

This is particularly the case for pyridine and diazine cycles (preferably metadiazine, see formulas below) and cycles which are derived therefrom, such as quinoline or isoquinoein, for example

More specifically the organic base comprising a saturated metalloid atom, having a resonance with a π bond can be advantageously chosen from dialkoyiaminopyridines, in particular in the para or ortho position (that is to say in the position 2 of pyridine or 4 see formula above).

Thus, said base carrying at least 2 trivalent nitrogen is advantageously such that said 2 trivalent nitrogen form a binding system comprising an imine conjugated with the doublet of an amine.

Amines which, like DBU (DiazaBicycloUndecene, which has 9 carbon atoms) or DBN (DiazaBicycloNonene which has 7 carbon atoms), form with the imine function a substituted amidine function, advantageously intracyclic with 1 or even 2 rings, constitute also particularly interesting bases for implementing the present invention. Examples of such bases are to be found in diazabicycloalkenes of 6 to 15 carbon atoms:

Five-membered rings are also of interest when they have two or three heteroatoms.

For example, structures of the imidazole, oxazole or cyclic, or even indolic, guanidine type:

R ₆ 'and R ₆ "have the same value as Rs. It is possible to substitute the free aryl vertices (engaged in an aromatic) or aliphatic (whose attachment point is a sp ³ carbon). But this is of little interest and the disadvantage of weighing down the base.

:

Pyrazole structures are also possible.

It should also be mentioned that among the non-cyclic structures, there may be a certain interest in using guanidine structures which have the characteristic of being easily derived from guanidine and of presenting a highly resonant formula:

where R ₆ "'and R ₆ ""are chosen from the same values as R ₆ ; they can be identical or different from the other R ₆ , as well as from R2- It is preferable if we want compounds with a low point of fusion that the molecule is asymmetrical. R ₆ '"and R ₆ ""can be linked together to form rings, advantageously aromatic. It is desirable for the molecular mass of the base to be at most 300, advantageously 250, more preferably 200. When the bases are polyfunctional (that is to say carry several basic systems as described above), these values must be brought back by basic function DA "= AR ₂ .

Another object of the present invention is to find a cycloaddition technique capable of working with the compounds of formula (I).

During the study which led to the present invention, it could be demonstrated that, provided that the environment is placed in relatively mild conditions, that is to say at a temperature below 150 ° C., preferably at most equal to 100 ° C., cycloadditions, or cyclocondensations, with a co-substrate carrying 2 double- bonds give good results and that their use gives cycles, in particular heterocycles substituted by a group R _f .

Although it is possible to make 2 + 4 type cycloadditions, one of the main interests of the present invention is to provide easy access to heterocycles by a 3 + 2 type addition, and in particular 1, 3 dipolar cycloadditions.

Advantageously, the co-substrate is an organic compound carrying a pentavalent nitrogen itself carrying 2 double bonds (including the donor-acceptor type bonds) of which at least one double bond connects said nitrogen to a carbon. In particular, the co-substrates providing the part of 3 atoms correspond to the canonical dipolar forms as follows:

© - ® -

- a - b - ç <- * - a = b - ç

Here b can be a nitrogen, optionally substituted, a and c can be oxygen, nitrogen or carbon, these last two atoms can carry a hydrocarbon radical or a hydrogen.

For this type of reaction, reference is made to the general work Advance Organic Chemistry, third edition, by JerryMarch, page 743 et seq., And to the documents cited in this reference book.

Heating these compounds gives, in the presence of a solvent or not, a cycloaddition even without a catalyst. However, some of the compounds whose canonical form was mentioned above must be synthesized in situ.

The nonlimiting examples below illustrate the invention.

Example 1 Dehydrohalogenation of the precursor CFgCHgCHCICHgOAc

Here R _f is trifluoromethyl, Ri and R ₃ are hydrogen and Ξ is chlorine.

(22)

The equation for the reaction is given below with some of the impurities identified:

φ co ço

JS c o ço

^" 3

Q.

Φ ω

.c: φ ϋ D3

Φ T3

Example 2 Dehydrohalogenation of the precursor CFaCHgCHCICHgOac in the presence of DM F

(2)

Example 3 Dehydrohalogenation of the precursor CFgCHgCHCICHgOAc using potassium carbonate

It has been shown that potassium carbonate makes it possible to carry out this dehydrochlorination reaction no longer at 25 ° C but at 60 ° C and in dipolar aprotic solvents such as DMF or NMP (ND = 27.3):

Effect of concentration: (DMF, K ₂ C0 ₃ (5 eq.), 60 ° C, 4 h)

(a) mass of (2) / mass of DMF (b) Determination by F-NMR with internal standard

Effect of the amount of KpCOg

(a) Assay by 19F NMR with PhOCF ₃ as an internal standard. Operating conditions: 60 ° C, 1 h, 3 g (15 mmof) of (2) for 28.5 g of DMF, depending on the stoichiometry in K ₂ C0 ₃ between 7 and 8.7% by weight.

Example 4 Dehydrohalogenation of the Precursor CFaCH _g CHBrCHgOAc

The dehydrobromation reaction is carried out without problem according to the same principle: CF ₃ CH ₂ CH (Br) CH ₂ OAc ^^ 'J ² ^ ³ > CF ₃ CH = CHCH ₂ OAc

60 ° C, t (h)

(2â) (3)

a) Test 02JGR910: test in RPAS 100 ml with double envelope, agitation: 4 inclined blades (600 rpm): 2a (10 g at 96% by weight, 38.5 mmol), DMF (35 g), K ₂ C0 ₃ (18 g, 0.130 mol), b)% CPG area

The reaction medium is left overnight at room temperature before treatment. After filtration (filtered glass No. 4) and washing of the cake with 10 ml of DMF, the filtrate is poured into 20 ml of water and this aqueous phase is extracted with MTBE (3 * 25 ml). The organic layer is assayed by ¹⁹ F NMR with internal standard:

Example 5 - Cycloaddition involving CFaCH≈CHCHgOAc

Synthesis of original heterocycles

rdt: 75% b)

TMS

Example 6 Dehydrochlorination with DBU

Synthesis of CF ₃ CH = CHCH ₂ OAc

2-chloro-4,4,4-trifluorobutyl acetate is charged into a 250 ml three-necked flask fitted with a condenser, a thermometer, an addition funnel and a magnetic stirrer (3a) (12 g 58.9 mmol) and diisopropyl ether (135 ml 0.95 mol). 1, 8-diazabicyclo [5.4.0] undec-7-ene (8.98 g 59 mmol) is added dropwise over 25 minutes. The reaction medium is heated at 70 ° C for 4 hours. The evolution is followed by CPG injections. At the end of the reaction, a yield of product formed of 77.5% is determined by GC assay with internal standard. The reaction medium is poured into 200 ml of water. Extraction is carried out with 3 times 100 ml of diisopropyl ether and the organic phases, previously grouped together, are dried over magnesium sulfate. After concentration at atmospheric pressure of the diisopropyl ether, 7 g (Yield: 71%) of the trifluorobutenol acetate are isolated by conventional distillation.

Example of dehydrobromation with KgCOa

An anhydrous NMP (10.25 g), potassium carbonate (5.13 g, 37.15 mmol) and then CF ₃ CH ₂ CHBrCH ₂ OAc (9) are introduced into a double-coated 100 ml reactor with mechanical agitation. , 13 g (78% by weight), 28.6 mmol (1 eq.)). The reaction medium is brought to 60 ° C for 4-6h. The evolution of the reaction is monitored by CPG (TT = 100%, RR = 95%).

At the end of the reaction, the trifluorobutenol acetate is distilled directly from the reaction medium. Peb = 45 ° C under 30 mBar. Structural characterization:

- Characteristic absorbances of the IR spectrum:.

1750 cm ^"1 vC≈O and 1230 cm ^{" 1} vC-O acetate function

1690 cm ^"1 vC = C and δC-H (out of plane) trans type unsaturation

1127 crτr ¹ vC-F - Chemical shifts of the proton, fluorine-19 and carbon-13 resonance lines (in CDCI ₃ ):

89.5% 10.5%

Chemical shifts ¹ H () Chemical shifts ¹⁹ F

Chemical shifts ¹³ C Example 7 - Valuation of CFaCH≈CHCHgOAc

(D (2)

In a 10 ml flask equipped with a condenser are added successively and at room temperature: 213 mg (1.27 mmol) of 4,4,4-trifluorobutenol acetate (93/7 E / Z, 100% by weight), 3 g of toluene and 228 mg (1.12 mmol) of N, α-diphenylnitrone (97% by weight). The solution is brought to reflux of the solvent (the nitrone is then quickly dissolved) for 26 hours. The toluene and the excess trifluorobutenol acetate are evaporated under reduced pressure and the product mixture of stereoisomers is obtained with a yield of 87% (ratio: (1) / (2), 25/1).

Claims

1. compound of formula (I):

in which: *> R _f is a radical carrying a perfluoromethylene group, which group ensures the bond with the rest of the molecule; *> R1 and R3, which may be the same or different, are chosen from hydrogen and alkyl or aryl radicals; *> Ψ is an electron-withdrawing group such that Ψ-OH is an acid whose pKa (in water) is at most equal to 8, advantageously 6, preferably 5.

2. Compound according to Claim 1, characterized in that Ψ is an electron-withdrawing group such that Ψ-O-H is an acid whose pKa (in water) is at least equal to 1, advantageously 2.

3. Compound according to Claims 1 and 2, characterized in that at least one of R1 and R3, is a light alkyl (at most 4 carbons) or a hydrogen, advantageously hydrogen.

4. Compound according to Claims 1 to 4, characterized in that the radical R _f is of formula (II):

GEA - (CX ₂ ) p- where:

- the X, identical or different, represent a chlorine, a fluorine or a radical of formula CnF2n + 1, with n integer at most equal to 5, preferably to 2, with the condition that the X of the methylene group carrying the bond open are not chlorines and at least one of them is fluorine;

- GEA is a hydrocarbon or electron-withdrawing group (that is to say that the Hammett constant σ _p (sigma p) is> 0, advantageously at least equal at 0.2, preferably inert, advantageously, when p is equal to 1, electron-withdrawing group; - p is a positive integer.

5. Compound according to claims 1 to 4, characterized in that R1 is hydrogen.

6. Compound according to claims 1 to 5, characterized in that R3 is hydrogen.

7. Compound according to claims 1 to 6, characterized in that R1 and R3 are hydrogen.

8. Compound according to Claims 1 to 7, characterized in that R _f is a perfluoroalcolyl of general formula CrF r + l where r is a positive integer ranging from

1 to 10, advantageously from 1 to 5, preferably from 1 to 3.

9. Compound according to Claims 1 to 8, characterized in that R _f is chosen from trifluoromethyl, pentafluoroethyl and heptafluoropropyl radicals.

10. Compound according to claims 1 to 8, characterized in that Ψ is an acyl.

11. Compound according to Claims 1 to 8, characterized in that Ψ is an acyl such that the pKa of Ψ-O-H is at least equal to approximately 2, advantageously

Ψ-O-H is an alkanoic acid with 1 to 8 carbon atoms, preferably 2 to 5.

12. Method for synthesizing a compound of formula (I), characterized in that it comprises bringing a compound of formula (III) into contact

Where Ξ is a leaving group chosen from psuedohalogens and halogens, advantageously chlorine or bromine; with a base chosen from strong nitrogenous bases whose associated acid has a pKa at least equal to 12 and / or from anionic bases with the condition that when the base is a non-nitrogenous anionic base the latter is in the presence of a solvent or a mixture of polar solvents.

13. The method of claim 12 characterized in that the base is a non-nitrogenous anionic base and in that said polar solvent has a solvent whose donor index is at least 10, advantageously 15, preferably 20.

14. The method of claims 12 and 13 characterized in that the base is a non-nitrogenous anionic base and in that said polar solvent is a solvent miscible with water in any proportion.

15. Method according to claims 12 to 14, characterized in that the base is a non-nitrogenous anionic base and in that said polar solvent does not have an acid function, that is to say that the pKa of the the most acidic hydrogen of said solvent is at least 20, advantageously 25, preferably 30.

16. The method of claim 12, characterized in that said base is an anionic nitrogen base, advantageously chosen from the salts, in particular alkali or alkaline-earth salts, of silylated amines and silylamines.

17. The method of claims 12 and 16, characterized in that said base is the anion of a silylamine chosen from alkali and alkaline earth salts of HMDZ (hexamethyldisilazane).

18. Method according to claims 12, 16 and 17, characterized in that said base is implemented in the presence of a polar solvent advantageously aprotic.

19. The method of claim 12, characterized in that said base is a carrier base of at least 2 trivalent nitrogen.

20. Method according to claims 12 and 19, characterized in that said base carrying at least 2 trivalent nitrogen is such that said 2 nitrogen are conjugated via at least one double bond.

21. The method of claims 12, 19 and 20, characterized by the wax that said base carrying at least 2 trivalent nitrogen is such that said 2 trivalent nitrogen form a binding system comprising an imine conjugated with the doublet of an amine .

22. Use of the compound of formula (I) as a heterocycle precursor substituted by a group R _f by cyclocondensation with a co-substrate carrying 2 double bonds.

23. Use according to claim 22, characterized in that said cyclocondensation is of type 3 + 2.

24. Use according to claims 22 and 23, characterized in that the co-substrate is an organic compound carrying a pentavalent nitrogen itself carrying 2 double bonds (including the donor-acceptor type bonds) including at least one double bond connects said nitrogen to a carbon.