WO2018154244A1

WO2018154244A1 - Method for the synthesis of pheromones

Info

Publication number: WO2018154244A1
Application number: PCT/FR2018/050422
Authority: WO
Inventors: Pierre Queval; Frédéric CAIJO; Mathieu ROUEN; Fabien TRIPOTEAU
Original assignee: Demeta
Priority date: 2017-02-24
Filing date: 2018-02-22
Publication date: 2018-08-30
Also published as: FR3063290A1

Abstract

The invention relates to a method for the synthesis of pheromones functionalised on one of the ends thereof and comprising at least two conjugated double bonds with a majority stereochemical configuration (E, Z). The reaction is carried out in two steps, comprising: (a) a metathesis reaction between a functionalised olefin and an unsaturated aldehyde, in the presence of at least one specific catalyst selected from the ruthenium complexes comprising a 1,3-diaryl-imidazolidin-2-yl ligand and a styrenyl ether ligand, and (b) the reaction of the product obtained in this way with a triphenylalkylphosphonium salt.

Description

PROCESS FOR SYNTHESIZING PHEROMONES

OBJECT OF THE INVENTION The present invention relates to a process for the synthesis of functionalized pheromones at one of their ends, comprising at least two conjugated double bonds of predominant stereochemical configuration (E, Z). The reaction is carried out in two steps, comprising: (a) a metathesis reaction between a functionalized olefin and an unsaturated aldehyde, in the presence of at least one particular catalyst selected from ruthenium complexes comprising a 1,3-diaryl ligand; imidazolidin-2-yl and a styrenylether ligand, and (b) reacting the product thus obtained with a triphenylalkylphosphonium salt.

BACKGROUND OF THE INVENTION The applications of synthetic pheromones have largely developed in recent years, in particular to control the populations of insects considered as harmful insofar as they negatively affect certain ecosystems (Asian Hornet), are vectors of diseases. (mosquitoes), ravage crops for food or feed or cause damage to property and health, especially in museums, homes and cities. In the agricultural field, pheromones are a biological alternative to synthetic pesticides that are likely to endanger the health of operators and the ecological balance. Pheromones are indeed natural molecules that, because of their volatility and their biodegradability, do not produce toxic residues. They also allow a very specific targeting of insects and therefore only affect the target populations.

One of the techniques that implements pheromones relies on sexual confusion; it consists of diffusing synthetic pheromones that mimic sexual pheromones from insect pests of crops. As a result, it is possible to mask the chemical communications between males and females and thus prevent their reproduction and the development of larvae on the crops. This technique is particularly suitable for viticulture and arboriculture. Another technique is that of mass trapping; it relies on the use of a pheromone to specifically attract a species of insects into a trap. Once trapped, the insect is removed by a small amount of insecticide, drowned or immobilized by glue. The advantage of this technique lies in the fact that the pesticide is no longer widespread on culture; it is no longer the product that goes to the insect, but the opposite. Other traps using pheromones are used not to eliminate insects but as a means of monitoring an insect population, in particular to map insects present in an area.

The techniques using pheromones remain to date relatively expensive, because of the small number of suppliers and the difficulties of synthesis of these compounds. This results in a relatively low product supply and relatively limited in terms of targeted insects, so the typology of crops to protect.

Among the pheromones listed to date, pheromones of type I lepidoptera are characterized by a linear structure with one or more unsaturations and an aldehyde function, alcohol or acetate in the terminal position. Within this group, many pheromones of interest have a structure containing two conjugated double bonds. This is particularly the case with codlemone, which is one of the only pheromones manufactured on a large scale (25 tonnes in 2010). This pheromone, which acts by sexual confusion, protects orchards against the codling moth of apples and pears. It is obtained in the form of a mixture of diastereoisomers of which only the diastereoisomer (E, E) is active. It is indeed well known that the effectiveness of pheromones depends on the stereochemistry of their double bonds. The codlemone synthesis methods can not be transposed to the synthesis of lepidopteranes of which only the (E, Z) isomer is active.

Among the synthetic routes proposed for obtaining these lepidopteranes, R.M. de Figueiredo et al. in J. Org. Chem. 2007, 72, 640-642 have suggested a double reaction of Wittig carried out on a dialdehyde using a phosphonium salt, followed by a second reaction of Wittig on the diènedial thus obtained, in the presence of a salt of alkyl phosphonium, leading to trienals which are then reduced to obtain a dienal of stereochemical configuration (E, Z) majority. This synthesis can not, however, be used to obtain pheromones other than aldehydes, in particular acetates or alcohols.

Moreover, a process for synthesizing a pheromone in the form of conjugated dienyl acetate of predominant (E, Z) configuration has been proposed in WO 2016/001383. This process comprises a step of phosphating an unsaturated aldehyde and then acylating the product thus obtained into presence of an iron catalyst. This process does not make it possible to prepare pheromones having other functional groups than esters.

Other methods have been described for preparing the same type of pheromones, but they have the disadvantage of including a large number of steps which necessarily impacts the production costs (PHG Zarbin et al., J. Braz, Chem. Vol 18, No. 6, 1100-1124, 2007; US-4,296,042; WO 01/00553; Khrimian et al., J. Agric Food Chem., Vol 56, 197-203, 2008). There is therefore still a need to have a process which makes it possible simply to synthesize, in a small number of steps, pheromones of the lepidopteran type, in the form of a functionalized conjugated diene, of stereochemical configuration (E, Z) which is the majority. It would also be desirable to have a process which is convergent, that is to say which makes it possible to obtain a variety of pheromones having different chain lengths and terminal functional groups.

The applicant has demonstrated that these needs could be met by implementing a two-step process combining a metathesis cross reaction, followed by a Wittig reaction.

It has already been suggested to carry out this succession of reactions to prepare compounds having a structure similar to that of the desired pheromones (RP Murelli et al., Org Lett Lett Vol 9, No. 9, 2007). However, this process which uses a stabilized phosphine leads to conjugated dienes of predominant (E, E) configuration. Above all, the method of Murelli et al. is not transposable to the synthesis of pheromones, in which the double bonds are generally separated from the functional group by several carbon atoms. The same is true of the very similar method described by T. Paul et al. for the preparation of 2,4-dienoates (Tetrahedron Letters, Vol. 48, 5367-5370, 2007). SUMMARY OF THE INVENTION

The inventors have developed a simple and inexpensive method making it possible to prepare, under economically advantageous conditions, pheromones of conjugated diene type functionalized at the end of the chain, with a stereochemical configuration (E _x , Z _x + ₂ ) which is the majority, or even with ratios (E / Z) _x and (Z / E) _x + ₂ each greater than 90: 10. The cost price and the efficiency of the pheromones obtained according to the invention can thus be improved by comparison with the processes. synthesis of pheromones known to date.

The subject of the invention is thus a process for the synthesis of pheromones, comprising the following successive stages:

a) the reaction of a compound of formula (I):

(I)

where X is a group selected from the groups -OH, -OCOR and -COOR where R denotes a C1-C6 alkyl group, A is an alkylene or alkenylene chain with n carbon atoms, where n is from 1 to 12 and W represents H or a C1-C3 alkyl group,

with a compound of formula (II):

(Π)

where R denotes a hydrogen atom or a C1-Cl2 alkyl group

in the presence of at least one catalyst selected from ruthenium alkylidene complexes comprising a 1,3-diarylimidazolidin-2-yl ligand and a styrenylether ligand,

to obtain a compound of formula (III):

(III)

where X and A have the meanings given above, wherein the double bond adjacent to A is predominantly of configuration (E); b) reacting the compound of formula (III) with a triphenylalkylphosphonium salt of formula (IV):

where Hal denotes a halide ion and m is an integer ranging from 0 to 7

to obtain a compound of formula (V):

(V)

where X, A and m have the meanings indicated above and the double bonds adjacent to A are predominantly of stereochemical configuration (E _x , Z _x + ₂ ), and

c) optionally, converting the compound of formula (V) into a compound of formula (VI) below:

(VI)

where A and m have the meanings indicated above, Y denotes a group chosen from the groups -OH, oxo, -CHO, -OCOR and -COOR where R denotes a C1-C6 alkyl group and the double bonds adjacent to A are predominantly of stereochemical configuration (E _x , Z _x + ₂ ).

DETAILED DESCRIPTION

The process according to the invention comprises a metathesis step of olefins followed by a Wittig reaction, in which these two steps are carried out under particular conditions.

The first of these steps consists in reacting a compound of formula (I):

(I) where X is a group selected from the groups -OH, -OCOR and -COOR where R denotes a C1-C6 alkyl group, A is an alkylene or alkenylene chain with n carbon atoms, where n is from 1 to 12 and W represents H or a C1-C3 alkyl group,

with a compound of formula (II):

(Π)

where R denotes a hydrogen atom or a C1-Cl2 alkyl group.

The compound of formula (I) may be commercially available, especially in the case of alkenyl acetates or certain alkenols, or it may alternatively be prepared from commercial sources following simple chemical reactions. Thus, the synthesis of fatty alkenyl esters can be carried out by esterification, using acetic acid, of a hydroxy-terminated α-olefin. The reaction is generally carried out in the presence of a strong acid, such as sulfuric acid, at a temperature of 40 to 80 ° C, for example 60 ° C. The product of formula (I) can then be recovered by extraction with a solvent and purified before being used in the process according to the invention. Other compounds of formula (I) may be prepared by esterification; this is particularly true of alkyl sorbate which can be prepared from sorbic acid. This compound is subjected to a metathesis reaction with an unsaturated aldehyde of formula (II), preferably acrolein or crotonaldehyde and more preferably acrolein, in the presence of at least one catalyst selected from ruthenium complexes comprising a 1,3-diaryl-imidazolidin-2-yl ligand and a styrenylether ligand. According to a preferred embodiment of the invention, the styrenylether ligand carries at least one electron-withdrawing group. By "electron-withdrawing group" is meant an attracting inductive effect group, that is to say having a higher electronegativity than that of carbon. The phenyl group of the styrenylether ligand can be substituted with, or condensed with, said electron-withdrawing group. According to the invention, it is preferred that the electron-withdrawing group be of the perhaloalkylcarbonylamido or alkoxycarbonylamido type, when it constitutes a substituent of the phenyl group and that it consists of an oxazine or of an oxazinone which is optionally hydrogenated when it is condensed in the grouping. phenyl (to thereby form a benzoxazine or benzoxazinone, respectively). The additional ligands of ruthenium are generally anionic ligands which may for example be independently selected from halides, benzoates, tosylates, mesylates, trifluoromethanesulfonates, pyrolides, trifluoroacetates, acetates, alcoholates and phenolates. It is preferred that they consist of halides and more particularly that they each designate a chlorine atom.

Among the catalysts of this type, mention may be made especially of the compounds of formula (VIIa):

(VIIa)

where X and X 'are anionic ligands advantageously chosen from those listed above; R1 and R2 independently denote a hydrogen atom, a C1-C6 alkyl group, a C5-C6 cycloalkyl group or a C5-C6 aryl group; R3 denotes a hydrogen atom, a C1-C6 alkyl group, a C5-C6 cycloalkyl group, a C5-C6 aryl group or a COR9 group, COOR9, CONHR9 or SO2R9 where R9 is a hydrogen atom, a C1-C6 alkyl group, a C5-C6 aryl or heteroaryl group optionally substituted with at least one substituent selected from C1-C6 alkoxy groups, C1-C6 alkyl pyridinium groups, NO2 group, CF3 group and halogen atoms; a, b and c independently denote a hydrogen atom or a C1-C6 alkyl group; Z represents a methylene or carbonyl group.

In a preferred embodiment, in formula (VIIa), R1 is a hydrogen atom; R2 is methyl, ethyl or isopropyl, preferably ethyl; R3 is a group -COOR9 where R9 is a C1-C6 alkyl group, preferably an isopropyl group; a, b and c denote a hydrogen atom; and Z is a carbonyl group.

Another group of catalysts that can be used in the metathesis step of the process according to the invention consists of the compounds of formula (VIIIb):

R8 R5

(VIIb)

where X and X 'are anionic ligands advantageously chosen from those described above; R4 denotes a hydrogen atom, a C1-C6 alkyl group, a C1-C6 perhaloalkyl group, an alkyl pyridinium group, a C1-C6 alkoxy group, a C5-C6 cycloalkyl group, a C5 aryl group; -C6 which is optionally substituted with at least one group selected from C1-C6 alkyl groups, halogen atoms and NO2 group; R5, R6, R7 and R8 independently denote a hydrogen atom, a C1-C6 alkyl group, a C5-C6 cycloalkyl group or a C5-C6 aryl group.

In one embodiment of the invention, in the formula (Vllb), R4 denotes a C 1 -C 6 alkoxy group or a CF 3 group, preferably a C 1 -C 6 alkoxy group; R5, R7 and R8 each denote a hydrogen atom; R6 is a C1-C6 alkyl group, preferably an isopropyl group.

The ligand L included in formulas (VIIa) and (VIIIb) corresponds to formula (VIII)

(VIII)

in which :

the groups Ra independently designate a C5-C6 aryl group which is unsubstituted or substituted by one or more groups chosen from C1-C6 alkyl groups, C1-C6 alkoxy groups, halogen atoms, in particular chlorine or fluorine, and C1-C6 perhaloalkyl groups, in particular CF3,

the Rb groups independently denote a hydrogen atom, a C1-C6 alkyl group, a halogen atom or a C5-C6 aryl group. According to the invention, it is preferred that Ra be selected from the group consisting of 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, 2,4,6-tris (trifluoromethyl) phenyl, 2,4,6-tris (trifluoromethyl) trichlorophenyl and hexafluorophenyl, preferably Ra is 2,6-diisopropylphenyl. In the context of this description, the term "C1-C6 alkyl group" means a linear or branched hydrocarbon chain containing from 1 to 6 carbon atoms. Examples of preferred alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl.

By "C5-C6 cycloalkyl" is meant a cyclic secondary aliphatic alkyl group, preferably a cyclopentyl or cyclohexyl group.

By "C1-C6 alkoxy" is meant a -O-C1-C6 alkyl group wherein the "C1-C6 alkyl" group is as defined above.

By "C5-C6 aryl" is meant a 5- or 6-membered carbocyclic group containing conjugated double bonds.

By "C5-C6 heteroaryl" is meant a 5- or 6-membered heterocyclic group containing 1 to 3 sulfur, nitrogen and / or oxygen atoms and conjugated double bonds.

By "halogen" is meant a fluorine, chlorine, bromine or iodine atom.

Examples of catalysts that can be used according to the invention are illustrated below.

wherein R = CF (M71-SiPr) or R = O-CH ₂ -CH (CH ₃ ) ₂ (M73-SiPr)

wherein R = CF ₃ (M71-SiMes) or R = O-CH ₂ -CH (CH ₃ ) ₂ (M73-SiMes)

M831

The ruthenium complexes of formula (VIIa) and (VIIIb) used according to the invention may, respectively, be prepared according to the processes described in US Pat. No. 8,835,628 and US Pat. No. 8,394,965.

In the synthesis method according to the invention, the amount of unsaturated aldehyde relative to the functionalized olefin of formula (I), expressed in moles, may for example be between 1: 1 and 5: 1 and it is Preferably, the amount of ruthenium complex relative to the functionalized olefin of formula (I), expressed in moles, may for example be between 100 and 50,000 ppm, preferably between 500 and 30,000 ppm and better still between 5,000 and 20,000 ppm. The metathesis process according to the invention can be carried out in the absence or in the presence of a solvent which can be any polar or apolar solvent such as water, acetone, ethyl acetate or dichloromethane. cyclohexane, benzene, toluene and mixtures thereof.

This process can advantageously be carried out under an inert atmosphere, in particular under a nitrogen or argon atmosphere, preferably at atmospheric pressure. Generally, a wide range of temperatures can be used. The reaction can thus be carried out at a temperature of 20 to 100 ° C, preferably 20 to 40 ° C. The duration of the reaction may also vary to a large extent and is for example between 1 minute and 24 hours, preferably between 30 minutes and 2 hours. The aforementioned metathesis reaction leads to a product containing a compound of formula (III)

(III)

where X and A have the meanings indicated above, which may or may not be concentrated and then purified, for example by chromatography on silica gel, before the implementation of the next step.

In formula (III), the double bond adjacent to A is predominantly of configuration (E). According to a preferred embodiment, the isomers of the compound of formula (III) are present in a ratio (E / Z) of at least 85: 15, preferably at least 90: 10 or even at least 95 5.

This product is then subjected to a Wittig reaction. For this purpose, the compound of formula (III) is brought into contact with a triphenylalkylphosphonium salt of formula (IV):

(IV)

where Hal denotes a halide ion and m is an integer from 0 to 7.

The compound of formula (IV) can be used in a molar ratio to the compound of formula (III) ranging for example from 1: 1 to 2: 1. The reaction is generally carried out in an organic solvent, such as THF or dioxane in the presence of a base such as sodium or potassium hydroxide, sodium or potassium alkoxide, sodium or potassium carbonate or hydrogen carbonate, sodium or potassium phosphate or sodium salt of lithium hexamethyldisilazane (NaHDMS, LiHDMS, KHDMS). It is preferred according to the invention to use a potassium alkoxide, in particular potassium tert-butanolate, in THF. The base is preferably introduced in equimolar amount relative to the triphenylalkylphosphonium salt. This reaction can be carried out at a temperature of 0 to 30 ° C and is advantageously carried out under an inert atmosphere.

At the end of this reaction, the reaction product is generally neutralized by addition of an organic or inorganic acid, such as hydrochloric acid, and then subjected to extraction using an organic solvent for recovering a purified organic phase, for example chromatography on silica gel, advantageously after filtration and concentration.

A compound of formula (V) is thus obtained:

(V)

where X, A and m have the meanings given above. In a first embodiment of the invention, the compound of formula (V) itself constitutes a pheromone.

Advantageously, the compound of formula (V) has one of the following definitions:

• X = -OCOR where R = -CH3; A is an alkylene chain with n carbon atoms in which n is from 1 to 12, preferably from 2 to 8, more preferably n = 6; m is an integer ranging from 0 to 7, preferably from 1 to 4, more preferably m = 1; so that it constitutes a dienyl ester;

X = -COOR with R is a C1-C6 alkyl group, preferably R = -CH3; A is an alkenylene chain with n carbon atoms in which n is from 1 to 12, preferably from 2 to 6, more preferably n = 2; m is an integer ranging from 0 to 7, preferably from 1 to 3, more preferably m = 2; so that it constitutes an alkyl trienoate.

In a second embodiment of the invention, the compound of formula (V) constitutes a pheromone precursor and the process according to the invention comprises one or more additional step (s) of transforming the compound of formula ( V) to a compound of formula (VI) below:

(VI)

where A and m have the meanings indicated above and Y denotes a group chosen from -OH, oxo, -CHO, -OCOR and -COOR groups where R denotes a C1-C6 alkyl group. In a first embodiment of this embodiment, the compound of formula (V) has the following definition: X = -OCOR where R denotes a C1-C6 alkyl group; A is an alkylene chain with n carbon atoms in which n is from 1 to 12, preferably n is from 5 to 10, more preferably n = 9; m is an integer ranging from 0 to 7, preferably from 1 to 3, more preferably m = 2; and is converted by hydrolysis to a compound of formula (VI) where Y = OH. It is thus possible to prepare pheromones in the form of polyunsaturated alcohols, in the case where the alcoholic reagent of formula (I) is not easily accessible. In this embodiment, the corresponding esters of formula (V) can be easily converted to alcohols by hydrolysis, according to methods well known to those skilled in the art.

In a second embodiment, the compound of formula (V) has the following definition: X = -COOR, where R is a C 1 -C 6 alkyl group, A is an alkylene or alkenylene chain with n carbon atoms where n is from 1 to 12; m is an integer from 0 to 7; and is converted by reduction into a compound of formula (VI) wherein Y = -CHO. This embodiment makes it possible to synthesize dienals from esters and using reducing agents well known to those skilled in the art, especially diisobutylaluminum hydride (DIBAL-H). The reduction reaction using DIBAL-H can in particular be carried out according to the process described by Dwivedi et al (Tet Asym 2011, 22, 1749-1756). In a third embodiment, the compound of formula (V) has the following definition: X = -OCOR; A is an alkylene chain with n carbon atoms in which n is from 1 to 12, preferably n is from 6 to 10, more preferably n = 7; m is an integer ranging from 0 to 7, preferably from 0 to 3, more preferably m = 2; and is converted by hydrolysis and then oxidation to a compound of formula (VI) where Y = oxo. This embodiment also makes it possible to synthesize dienals, which constitute a particularly desired class of pheromones, from alcohols or esters, according to reactions well known to those skilled in the art, in particular by Swern oxidation. in the presence of oxalyl chloride, DMSO and an amine base, or Parikh-Doering oxidation in the presence of pyridine-sulfur trioxide complex (Pyr.SO ₃ ), DMSO and a base of the type amine.

The pheromone or the pheromone precursor may optionally be subsequently distilled. A compound having a purity of more than 90% or even more than 95% or even more than 99%) is thus recovered, as measured by gas chromatography. Alternatively, the pheromone or pheromone precursor obtained according to the invention can be purified by other techniques than distillation and especially by recrystallization in a solvent, filtration, silica gel chromatography or a combination of these techniques. The pheromones or pheromone precursors thus obtained are predominantly of stereochemical configuration (E _x , Z _x + ₂ ). According to a preferred embodiment, they have a ratio (E / Z) x of at least 85: 15, preferably at least 90: 10 or even at least 95: 5 and a ratio (Z / E _x + ₂ of at least 80:20 or even 90:10.

In the expressions (E _x , Z _x + ₂ ), (E / Z) _x , (Z / E) _x + ₂ :

the index x denotes the double bond adjacent to the chain A in formulas (V) and (VI);

the index x + 2 denotes the double bond conjugated to the double bond designated by the index x and not included in the chain A, in the formulas (V) and (VI).

The expression (E _x , Z _x + ₂ ) means that the double bond designated by the index x is of configuration E and the double bond designated by the index x + 2 is of configuration Z.

These pheromones may be useful in making traps or dispersed on crops to protect them. Examples of use of some pheromones obtainable according to the invention are given below:

Ravaging pheromone

(E, Z) -7,9-dodecadienyl acetate Lobesia botrana

(E, Z) -3,5-dodecadienyl acetate Bonagota cranaodes

(E, Z) -3,5-tetradecadienyl acetate Recurvaria leucatella

(E, Z) -8,10-pentadecadienyl acetate Acrobasis vaccinii

(E, E, Z) -2,4,6-methyl decatrienoate Halyomorpha halys; Plautia stali

(E, Z) -7,9-dodecadien-1-ol Lobesia botrana

(Ε, Ζ) - 10, 12-hexadecadien-1-ol Bombyx mori

(E, Z) -7,9-dodecadien-1 -al Idaea biselata

(E, Z) -8,10-dodecadien-1 -al Acria ceramitis

(E, Z) -8,10-tetradecadien-1 -al Cameraria ohridella (horse chestnut leafminer)

(E, Z) -9,11-hexadecadien-1-al Acrobasis nuxvorella; Diatraea saccharalis

(Ε, Ζ) - 10, 12-hexadecadien-1 -al Coloradia pandora

(E, Z) - 11, 13-hexadecadien-1 -al Notodonta dromedarius EXAMPLES

The invention will be better understood in the light of the following examples, which are given purely by way of illustration and are not intended to limit the scope of the invention, defined by the appended claims.

Material and methods

The experiments under an inert atmosphere (dinitrogen or argon) were carried out using glassware previously dried in an oven. The dichloromethane (stabilized on amylene) was dried over calcium hydride and then distilled before being used. Tetrahydrofuran (THF) was dried over sodium / benzophenone and distilled before use. Commercial reagents were used as received. Acrolein is from Sigma-Aldrich (90%, stabilized with hydroquinone). The 1 H NMR (300 MHz) and ¹³ C (75 MHz) spectra were recorded on Bruker ARX400 and ARX300 spectrometers. The chemical shifts (δ) are expressed in parts per million (ppm) using the resonance signal of the solvent as internal reference (CDCb, ¾: δ 7.26 ppm, ¹³ C: δ 77.16 ppm). The following abbreviations are used: s = singlet, t = triplet, qi = quintuplet, sex = sextuplet, td = triplet of doublets, ddd = doublets of doublets of doublets, m = multiplet, etc. The coupling constants (J) are expressed in Hertz (Hz). Analyzes by gas chromatography (GC) were performed on a Shimadzu GC-2014 ^® spectrometer equipped with a column DB-23 ^® and Agilent ^® Shimadzu GCMS-QP2010-SE column equipped with a Zebron ZB-5MSÏ ^®.

The catalysts used in the examples which follow correspond to the formula below:

wherein R = CF ₃ (M71-SiPr) or R = O-C (CH ₃ ) ₃ (M73-SiPr). Example 1 Synthesis of (E, Z) -7,9-dodecadienyl acetate (E7Z9-12Ac).

7-8Ac (1.15 mL, 6.0 mmol), acrolein (0.89 mL, 12 mmol) and dichloromethane (6 mL) are added to a dry flask and argon is bubbled through. mixing for 2 minutes. M73-SIPr catalyst (50 mg, 0.06 mmol) is introduced and argon is bubbled into the mixture for 1 minute. The mixture is then stirred at 40 ° C for 3 hours under argon. After returning to ambient temperature, the mixture is concentrated under reduced pressure and then purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate with a gradient of 9/1 and 8/2). The product E7Ad19-9Ac is then obtained in the form of a brown oil (958 mg, 81%, E / Z mixture = 97/3). ¹ U NMR (CDCl 3, 300 MHz): δ (for the E isomer) 9.50 (d, ³ / HH = 7.9 Hz, 1H); 6.84 (dt, ³ Ju- _ra n _S = 15.6 Hz, ³ / HH = 6.8 Hz, 1H); 6.11 (ddt, ³ Juans = 15.6 Hz, ³ _H -H = 7.9 Hz, ⁴ / HH = 1.5 Hz, 1H); 4.05 (t, ³ / HH = 6.7 Hz, 2H); 2.40-2.28 (m, 2H); 2.04 (s, 3H), 1.71 (m, 2H); 1.71-1.45 (m, 2H); 1.45-1.30 (m, 4H).

1-Propyltriphenylphosphonium bromide (2.23 g, 5.8 mmol) and potassium ie / t-butanolate (0.65 g, 5.8 mmol) are introduced into a flask and empty cycles / argon are applied . THF (15 mL) and added at room temperature and the mixture stirred for 1 h under argon. E7Ald9-9Ac (0.95 g, 4.8 mmol) dissolved in THF (5 mL) is added at 0 ° C and the mixture is stirred at room temperature for 1 h. 1N hydrochloric acid (20 mL) is added and the phases are separated. The aqueous phase is extracted with ethyl acetate (20 mL). The organic phases are combined and then washed with a saturated solution of sodium chloride (20 mL), dried over magnesium sulfate, filtered on cotton and then concentrated under reduced pressure. The crude product is purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate with a 95/5 gradient). The pheromone E7Z9-12Ac is then obtained in the form of a pale yellow oil (803 mg, 74%, EZ / EE / ZZ / ZE mixture = 86/10/3/1, purity (GC)> 99%). ¹ H NMR (CDCl 3, 300 MHz): δ (for the ET-isomer) 6.34-6.24 (m, 1H); 5.96-5.85 (m, 1H); 5.64 (dt, ³ m Ju-year _r _S = 14.5 Hz, ³ / HH = 7.0 Hz, 1H); 5.30 (dt, JH-Hds = 10.8 Hz, ³ / HH = 7.5 Hz, 1H); 4.05 (t, ³ / HH = 6.7 Hz, 2H); 2.24-2.14 (m, 2H); 2.14 - 2.04 (m, 2H); 2.04 (s, 3H); 1.68-1.54 (m, 2H); 1.47-1.28 (m, 6H); 0.99 (t, ³ / HH = 7.5 Hz, 3H). ¹³ C NMR (CDCl 3, 75 MHz): δ (for the ET isomer) 171.3; 134.4; 132.2; 128.1; 125.7; 64.7; 32.8; 29.3; 28.9; 28.6; 25.9; 21.1; 14.4. Example 2 Synthesis of (E, Z) -7,9-dodecadienyl acetate (E7Z9-12Ac) directly.

Acrolein (1 equiv.)

M73-SIPr (1.5 mol%) t-BuOK Ph ₃ Br (1.2 equiv.)

CH _j Cpp 40 ° C, 2h30 THF, 0 ° C puid TA, 1h

E7-Ald9-9Ac

7-8Ac (0.96 mL, 5.0 mmol), acrolein (0.37 mL, 5.0 mmol) and dichloromethane (5 mL) are added to a dry flask. M73-SIPr catalyst (62 mg, 0.075 mmol) is introduced and the mixture is then stirred at 40 ° C for 2 h under argon. After returning to ambient temperature, the mixture is concentrated under reduced pressure. The crude product is then obtained in the form of a brown oil (1.06 g, conversion = 93%, ratio E / Z = 97/3). 1-Propyltriphenylphosphonium bromide (2.31 g, 6.0 mmol) and potassium iert-butanolate (0.67 g, 6.0 mmol) are charged to a flask and vacuum / argon cycles are applied. THF (15 mL) is added at room temperature and the mixture is stirred for 1 hour under argon. The crude product obtained in the previous step (1.06 g) dissolved in THF (5 mL) is added at 0 ° C. and the mixture is then stirred at room temperature for 1 h. 1N hydrochloric acid (20 mL) is added and the phases are separated. The aqueous phase is extracted with ethyl acetate (20 mL). The organic phases are combined and then washed with a saturated solution of sodium chloride (25 mL), dried over magnesium sulfate, filtered on cotton and then concentrated under reduced pressure. The crude product is purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate with a gradient 100/0 then 99/1 and 90/10). The pheromone E7Z9-12Ac is then obtained in the form of a pale yellow oil (733 mg, 65%, EZ / EE / ZZ / ZE mixture = 86 / 12/1 / traces, purity (GC)> 95%). Example 3 Synthesis of (E, Z) -8,10-tetradecadienal (E8Z10-14Ad1).

In a dry flask under argon, 8-9Ac (0.88 mL, 5.43 mmol), acrolein (0.8 mL, 10.85 mmol) and dichloromethane (6 mL) are introduced. The solution is degassed by bubbling with argon for 2 minutes and the M73-SIPr catalyst (22.4 mg, 0.027 mmol) is added. After 1 minute of bubbling with argon, the reaction is stirred at 40 ° C under argon for 3 hours. The solvent is evaporated and the crude reaction product is purified by flash chromatography on silica gel (eluent: cyclohexane / ethyl acetate) to yield the compound E8Ad1010Ac (940 mg, 82%, E / Z mixture = 98/2) in the form of a pale yellow oil. NMR ¾ (CDCl 3, 300 MHz): δ (for the E isomer) 9.51 (dt, J = 8.0 and 1.1 Hz, 1H); 6.86 (dt, J = 15.6 and 8.0 Hz, 1H); 6.12 (ddt, J = 15.6, 8.0 and 1.1 Hz, 1H); 4.06 (tt, J = 6.8 and 1.1 Hz, 2H); 2.35 (tdd, J = 7.8, 6.2 and 1.3 Hz, 2H); 2.05 (t, J = 1.0 Hz, 3H); 1.72-1.45 (m, 4H); 1.41-1.30 (m, 6H).

1-Butyltriphenylphosphonium bromide (2.1 g, 5.26 mmol) and potassium e / t-butanolate (589 mg, 5.26 mmol) are charged to a flask and vacuum / argon cycles are applied. THF (18 mL) and added at room temperature and the mixture is stirred for 1 h under argon. E8Δld10-10Ac (930 mg, 4.38 mmol) dissolved in THF (12 mL) is added at 0 ° C and the mixture is stirred at 0 ° C at room temperature for 3 h. 1N hydrochloric acid (40 mL) is added and the phases are separated. The aqueous phase is extracted with ethyl acetate (40 mL). The organic phases are combined and then washed with a saturated solution of sodium chloride (30 ml), dried over magnesium sulfate, filtered on cotton and then concentrated in vacuo. The crude product is purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate 9/1). The product E8Z10-14Ac is then obtained in the form of a colorless oil (902 mg, 82%, EZ / EE / ZZ / ZE mixture = 90/8/1 / traces, purity (GC)> 97% .RMN ^1). U (CDCl 3, 300 MHz): δ (for the ET-isomer) 6.39-6.26 (m, 1H), 6.03-5.91 (m, 1H), 5.67 (dt, J = 14.5 and 7.0 Hz, 1H), 5.33 (dt, J = 10.8 and 7.6 Hz, 1H), 4.07 (t, J = 6.7 Hz, 2H); 22-2.07 (m, 4H), 2.06 (s, 3H), 1.69-1.56 (m, 2H), 1.48-1.25 (m, 10H), 0.94 (m, 2H); t, J = 7.3 Hz, 3H).

To a solution of NaOH (675 mg, 16.89 mmol) in methanol (10 mL) is added a solution of E8Z10-14Ac (900 mg, 3.38 mmol) in THF (5 mL). The reaction medium is stirred at 40 ° C. for 20 hours. After returning to ambient temperature, the solvents are evaporated under reduced pressure. The residue is diluted with water (20 mL) and extracted with cyclohexane (20 mL). The organic phase is washed with water and then with a saturated aqueous solution of NaCl (10 mL), dried over MgSO ₄ , filtered and concentrated under reduced pressure to give the compound E8Z10-140H (685 mg, 91%) in the form a pale yellow oil. ¹ H NMR (CDCl 3, 300 MHz): δ (for the ET isomer) 6.38-6.26 (m, 1H); 6.02-5.92 (m, 1H); 5.67 (dt, J = 14.5 and 7.0 Hz, 1H); 5.32 (dt, J = 10.8 and 7.5 Hz, 1H); 3.66 (t, J = 6.6 Hz, 2H); 2.21-2.06 (m, 4H); 1.65-1.53 (m, 2H); 1.48-1.29 (m, 10H); 0.94 (t, J = 7.3 Hz, 3H).

In a dry flask under argon, E8Z10-14OH (685 mg, 3.25 mmol), DMSO (20 mL) and triethylamine (3.63 mL, 26.05 mmol) are introduced. A solution of Pyridine-SO 3 (2.6 g, 16.28 mmol) in DMSO (10 mL) is added dropwise and the reaction medium is stirred at room temperature under an argon atmosphere for 3 hours. The solution is diluted in ethyl acetate (40 mL). The organic phase is washed with water (40 mL), dried over MgSO4, filtered and concentrated under vacuum. The crude mixture is purified by chromatography on silica gel (eluent: cyclohexane / ethyl acetate 95/5 and then 9/1) to give the pheromone E8Z10-14Ald (560 mg, 83%, EZ / EE / ZZ mixture). ZE = 90/8/1 / traces, purity (GC)> 99.5%) as a colorless oil. NMR ¾ (CDCl 3, 300 MHz): δ (for the ET isomer) 9.76 (t, ³ / H-HAW = 1.8 Hz, 1H); 6.36-6.24 (m, 1H); 5.95 (t, ³ / HH = 10.9 Hz, 1H); 5.63 (dt, ³ Juans = 14.6 Hz, ³ _H -H = 7.0 Hz, 1H); 5.30 (dt, ³ / HH + _s = 10.8 Hz, ³ / HH = 7.5 Hz, 1H); 2.42 (td, ³ / HH = 7.3 Hz, ³ / H-HAW = 1.8 Hz, 1H); 2.20-2.04 (m, 4H); 1.69-1.56 (m, 2H); 1.48-1.27 (m, 8H); 0.91 (t, ³ / HH = 7.3 Hz, 1H). ¹³ C NMR (CDCl 3, 75 MHz): δ 203.0; 134.4; 130.1; 128.8; 126.0; 44.0; 32.9; 29.9; 29.3; 29.1; 29.0; 23.0; 22.2; 13.9.

Example 4: Synthesis of (E, Z) -10,12-hexadecadien-1-ol (E10Z12-16OH).

10-undecen-1-ol (10-11OH) (1.77 mL, 8.85 mmol), acetic acid (5.1 mL, 88.3 mmol) and concentrated sulfuric acid (1 drop (4 μl), 0.1 mmol) are introduced into a flask and the mixture is stirred at 60 ° C. for 2 h. After returning to ambient temperature, ethyl acetate (15 mL) is added and a saturated aqueous solution of sodium carbonate (30 mL) is added slowly and the mixture is stirred vigorously for 15 minutes. The phases are separated and the organic phase is washed successively with a saturated aqueous solution of sodium carbonate (10 mL) and then with a saturated aqueous solution of sodium chloride (10 mL). The organic phase is dried over magnesium sulfate, filtered through cotton and then passed over alumina and the solvent is removed under reduced pressure. The product 10-HAc is obtained in the form of a colorless oil (1.84 g, 98%). ¹ U NMR (CDCb, 300 MHz): δ 5.87-5.72 (m, 1H); 5.03-4.88 (m, 2H); 4.04 (t, ³ / HH = 6.8 Hz, 2H); 2.09-1.97 (m, 2H); 2.03 (s, 3H); 1, 66-1, 54 (m, 2H); 1, 43-1, 21 (m, 12H).

10-llAc (1.07 mL, 5.0 mmol), acrolein (0.75 mL, 10 mmol) and dichloromethane (5 mL) are added to a dry flask and argon is bubbled through. mixing for 2 minutes. M73-SIPr catalyst (21 mg, 0.025 mmol) is introduced and argon is bubbled into the mixture for 1 minute. The mixture is then stirred at 40 ° C. for 5 hours under argon. After returning to ambient temperature, the mixture is concentrated under reduced pressure and then purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate with a 95/5 gradient then 9/1 and 8/2). The product E10A1212-12Ac is then obtained in the form of a pale yellow oil (934 mg, 70%, E / Z mixture = 97/3). ¹ U NMR (CDCl 3, 300 MHz): δ (for the E isomer) 9.49 (d, ³ / HH = 7.9 Hz, 1H); 6.84 (dt, ³ / HH = 15.6 Hz, ³ / HH = 6.8 Hz, 1H); 6.16-6.05 (m, 1H); 4.04 (t, ³ / HH = 6.8 Hz, 2H); 2.39-2.26 (m, 2H); 2.03 (s, 3H); 1.66-1.55 (m, 2H); 1, 55-1, 44 (m, 2H); 1.39-1.22 (m, 10H).

1-Butyltriphenylphosphonium bromide (1.84 g, 4.6 mmol) and potassium ie / t-butanolate (0.51 g, 4.6 mmol) are introduced into a flask and empty cycles / argon are applied. . THF (16 mL) and added at room temperature and the mixture stirred for 1 h under argon. E10A1212-12Ac (633 mg, 2.6 mmol) dissolved in THF (3 mL) is added at 0 ° C and the mixture is stirred at room temperature for 1 h 30 min. 1N hydrochloric acid (20 mL) ) is added and the phases are separated. The aqueous phase is extracted with ethyl acetate (30 mL). The organic phases are combined and then washed with a saturated solution of sodium chloride (20 mL), dried over magnesium sulfate, filtered on cotton and then concentrated under reduced pressure. The crude product is purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate 9/1). The product E10Z12-16Ac is then obtained in the form of a pale yellow oil (540 mg, 74%, EZ / EE / ZZ / ZE mixture = 92/6/1 / traces, purity (GC) = 98%). NMR ¾ (CDCl 3, 300 MHz): δ (for the EX isomer) 6.36-6.24 (m, 1H); 6.00-5.90 (m, 1H); 5.65 (dt, ³ JH-m _ra ™ = 14.5 Hz, ³ / HH = 7.0 Hz, 1H); 5.30 (dt, ³ / HH + _s = 10.7 Hz, ³ / HH = 7.5 Hz, 1H); 4.05 (t, ³ / HH = 6.7 Hz, 2H); 2.20-1.88 (m, 4H); 2.04 (s, 3H); 1, 67-1, 54 (m, 2H); 1.45-1.23 (m, 14H); 0.90 (t, ³ / HH = 7.4 Hz, 3H). E10Z12-16Ac (530 mg, 1.88 mmol) and THF (3 mL) are added to a flask. A solution of sodium hydroxide (381 mg, 9.5 mmol) in methanol (6.3 mL) is added at room temperature and the mixture is stirred at 40 ° C for 4 h. The mixture is concentrated under reduced pressure and water (10 mL) is added. The aqueous phase is extracted with cyclohexane (2 x 10 mL). The organic phases are combined and then washed with a saturated aqueous solution of sodium chloride (10 mL), dried over magnesium sulfate, filtered on cotton and concentrated under reduced pressure. The pheromone E10Z12-16OH is obtained in the form of a pale yellow oil (448 mg, 100%, EZ / EE / ZZ / ZE mixture = 92/6/1 / traces, purity (GC)> 99.5%) . ¹ H NMR (CDCl 3, 300 MHz): δ (for the ET isomer) 6.36-6.24 (m, 1H); 5.96 (t, ³ / HH = 10.9 Hz, 1H); 5.65 (dt, ³ / HH = 14.5 Hz, ³ / HH = 7.0 Hz, 1H); 5.30 (dt, ³ / HH = 10.9 Hz, ³ / HH = 7.6 Hz, 1H); 3.63 (t, ³ / HH = 6.6 Hz, 2H); 2.20-2.04 (m, 4H); 1.62-1.50 (m, 2H); 1.45-1.23 (m, 15H); 0.92 (t, ³ / HH = 7.3 Hz, 3H). ¹³ C NMR (CDCl 3, 75 MHz): δ (for the ET isomer) 134.4; 129.6; 128.7; 125.5; 76.5; 62.5; 32.7; 32.5; 29.6; 29.4; 29.3i; 29.2? ; 29.1; 25.6; 22.7; 13.6.

Example 5 Synthesis of methyl (E, E, Z) -2,4,6-decatrienoate (me-E2E4Z6-decatrienoate)

Sorbic acid Methyl sorbate E2E4-Ald5-6COOMe Sorbic acid (1.12 g, 10 mmol), methanol (50 mL) and para-toluenesulfonic acid (95 mg, 0.5 mmol) are introduced. in a flask and the mixture is stirred at 60 ° C for 28 h. The mixture is concentrated under reduced pressure and the crude residue is purified by flash chromatography on silica gel (eluent cyclohexane / ethyl acetate 9/1). The methyl sorbate is obtained in the form of a colorless oil (814 mg, 65%). NMR ¾ (CDCl 3, 300 MHz): δ 7.29-7.21 (m, 1H); 6.23-6.08 (m, 2H); 5.77 (dd, ³ Ju-mra = 15.4 Hz, ⁴ / HH = 0.6 Hz, 1H); 3.73 (s, 3H); 1.85 (dd, ³ Ju-m _ra ns = 5.9 Hz, ⁴ / HH = 0.5 Hz, 1H).

Methyl sorbate (804 mg, 6.38 mmol), acrolein (0.95 mL, 12.8 mmol) and dichloromethane (6.5 mL) are introduced into a dry flask and argon is added. bubbled in the mixture for 5 minutes. M71-SIPr catalyst (26 mg, 0.032 mmol) is introduced and the mixture is then stirred at 40 ° C for 4 hours under argon. Acrolein (0.95 mL, 12.8 mmol) and then a solution of M71-SIPr catalyst (26 mg, 0.032 mmol) in dichloromethane (13 mL) are introduced and the mixture is then stirred at 40 ° C. for 16 h under argon. After returning to ambient temperature, the mixture is concentrated under reduced pressure and then purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate with a 9/1 and then 7/3 gradient). The product E2E4-Ald5-6COOMe is then obtained in the form of a pale brown solid (206 mg, 23%, EE / EZ mixture = 97/3, purity (GC)> 99%). NMR ¾ (CDCb, 300 MHz): δ (for the EE isomer) 9.67 (d, ³ / HH = 7.7 Hz, 1H); 7.43 (ddd, ³ Ju-m _r _S = 15.4 Hz, ³ / HH = 11.3 Hz, ⁴ / HH = 0.7 Hz, 1H); 7.17 (ddd, ³ Ju-m _ra n _S = 15.5 Hz, ³ / HH = 11.3 Hz, ⁴ / HH = 0.8 Hz, 1H); 6.42 (dd, ³ Juans = 15.5 Hz, ³ / HH = 7.7 Hz, 1H); 6.31 (d, ³ m _Ju-ng _S = 15.4Hz, 1H); 3.80 (s, 3H). 1-Butyltriphenylphosphonium bromide (686 mg, 1.72 mmol) and potassium β-tert.-butanolate (193 mg, 1.72 mmol) are added to a flask and vacuum / argon cycles are applied. THF (5 mL) and added at room temperature and the mixture stirred for 2 h under argon. E2E4-Ald5-6COOMe (200 mg, 1.43 mmol) dissolved in THF (4 mL) is added at 0 ° C and the mixture is stirred at room temperature for 1 h. 1N hydrochloric acid (10 mL) is added and the phases are separated. The aqueous phase is extracted with ethyl acetate (10 mL). The organic phases are combined and then washed with a saturated solution of sodium chloride (10 mL), dried over magnesium sulfate, filtered on cotton and then concentrated under reduced pressure. The crude product is purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate 9/1). The me-E2E4Z6-decatrienoate pheromone is then obtained in the form of a pale orange oil (203 mg, 79%, EEZ / EEE / EZZ / ZZZ mixture = 80/17/2/1, purity (GC) = 91% ). ¹ H NMR (CDCl 3, 300 MHz): δ (for the EEZ isomer) 7.40-7.32 (m, 1H); 6.90-6.81 (m, 1H); 6.34-6.25 (m, 1H); 6.14-6.06 (m, 1H); 5.90-5.82 (m, 1H); 5.74-5.65 (m, 1H); 3.75 (s, 3H); 2.26 - 2.18 (m, 2H); 1.46 (sex, ³ / HH = 7.4 Hz, 2H); 0.93 (t, ³ / HH = 7.4 Hz, 3H). ¹³ C NMR (CDCl 3, 100 MHz): δ (for the EEZ isomer) 167.6; 145.1; 137.6; 136.2; 129.7; 128.2; 120.1; 51.5; 30.2; 22.7; 13.8.

Example 6 Synthesis of E7Ald9-9Ac Aldehyde (precursor (E, Z) -7,9-dodecadienyl acetate (E7Z9-12Ac)) from crotonaldehyde.

7-8Ac (0.23 mL, 1.2 mmol), crotonaldehyde (0.10 mL, 1.2 mmol) and dichloromethane (1.2 mL) are added to a dry flask and argon is added. bubbled in the mixture for 2 minutes. M73-SIPr catalyst (15 mg, 0.018 mmol) is introduced and argon is bubbled into the mixture for 1 minute. The mixture is then stirred at 40 ° C. for 4 hours under argon. After returning to ambient temperature, the mixture is concentrated under reduced pressure and purified by chromatography on silica gel (eluent cyclohexane / ethyl acetate with a gradient of 9/1 and 8/2). The product E7Ald9-9Ac is then obtained in the form of a pale yellow oil (150 mg, 63%, E / Z mixture = 98/2). ¹ H NMR (CDCl 3, 300 MHz): δ (for the E isomer) 9.50 (d, ³ / H) H = 7.9 Hz, 1H); 6.84 (dt, ³ J _H -m ™ _ra = 15.6 Hz, ³ / HH = 6.8 Hz, 1H); 6, 1 1 (ddt, ^3-jR m _rans = 15.6 Hz, ³ / HH = 7.9 Hz, ⁴ / HH = 1, 5 Hz, 1H); 4.05 (t, ³ / HH = 6.7 Hz, 2H); 2.40-2.28 (m, 2H); 2.04 (s, 3H), 1.71 (m, 2H); 1.71-1.45 (m, 2H); 1.45-1.30 (m, 4H). This intermediate can then be converted into E7Z9-12Ac by a Wittig reaction as described in Example 2. EXAMPLE 7 Synthesis of the Aldehyde E8Ald10-10Ac ((E, Z) -8,10-tetradecadienal precursor ( E8Z10-14Ald) from crotonaldehyde.

In a dry flask under argon, 8-9Ac (0.25 mL, 1.2 mmol), crotonaldehyde (0.20 mL, 2.4 mmol) and dichloromethane (1.2 mL) are introduced. The solution is degassed by bubbling with argon for 2 minutes and M73-SIPr catalyst (5 mg, 0.006 mmol) is added. After 1 minute of bubbling with argon, the reaction is stirred at 40 ° C under argon for 4 hours. The solvent is evaporated and the crude reaction product is purified by flash chromatography on silica gel (eluent: cyclohexane / ethyl acetate) to yield compound E8Ad1010Ac in the form of a pale yellow oil (174 mg, 69%, E / Z mixture = 99/1). NMR ¾ (CDCl 3, 300 MHz): δ (for the E isomer) 9.51 (dt, J = 8.0 and 1.1 Hz, 1H); 6.86 (dt, J = 15.6 and 8.0 Hz, 1H); 6.12 (ddt, J = 15.6, 8.0 and 1.1 Hz, 1H); 4.06 (tt, J = 6.8 and 1.1 Hz, 2H); 2.35 (tdd, J = 7.8, 6.2 and 1.3 Hz, 2H); 2.05 (t, J = 1.0 Hz, 3H); 1.72-1.45 (m, 4H); 1.41-1.30 (m, 6H). This intermediate can then be converted into E8Z10-14Ald by a succession of reactions as described in Example 3.

Comparative Example: Influence of Metathesis Catalyst on Conversion Rate

(E, Z) -8,10-tetradecadienal was synthesized similarly to Example 2, using different types of metathesis catalysts.

To do this, 8-9Ac (0.088 mL, 0.54 mmol), acrolein (0.08 mL, 1.08 mmol) and dichloromethane (0.5 mL) are introduced into a dry flask under argon. . The solution is degassed by bubbling with argon for 2 minutes and a solution 27.1 mM of catalyst in dichloromethane (0.1 mL, 0.0027 mmol) is added. After 1 minute of bubbling with argon, the reaction is stirred at 40 ° C under argon for 22 hours. The solvent is evaporated and the reaction crude is analyzed by proton NMR to determine the conversion.

The various catalysts below have been tested:

OCSC6-lPr 7i OCSC6-lMesM7i The following conversion rates were obtained:

As can be seen from this table, the catalysts according to the invention (last four rows of the table) make it possible to achieve a higher conversion rate than catalysts which do not exhibit a styrenyl ether ligand (Grubbs II, M2 and CatMetium RF1) or of 1,3-diarylimidazolidin-2-yl ligand (C6-iPr M71 and C6-Imes M71). The conversion rate is also significantly higher than that obtained with a catalyst whose styrenyl ether ligand does not carry an electron-withdrawing group (HG II). This effect is particularly pronounced for the catalysts according to the invention in which the 1,3-diaryl-imidazolidin-2-yl ligand is N, N-disubstituted with a 2,6-diisopropylphenyl group (M71-SiPr and M73-SiPr). Among these, the conversion rate is maximum when using a metathesis catalyst carrying an alkoxycarbonylamido type electron-withdrawing group.

Claims

A process for synthesizing pheromones, comprising the following successive steps:

a) the reaction of a compound of formula (I):

(I)

with a compound of formula (II):

(II)

where R denotes a hydrogen atom or a C1-Cl2 alkyl group

to obtain a compound of formula (III):

(III)

where X and A have the meanings given above and the double bond adjacent to A is predominantly of configuration (E);

b) reacting the compound of formula (III) with a triphenylalkylphosphonium salt of formula (IV):

(IV)

where Hal denotes a halide ion and m is an integer ranging from 0 to 7

to obtain a compound of formula (V):

(V)

(VI)

2. Method according to claim 1, characterized in that said ruthenium complex is chosen from compounds of formula (VIIa:

"3

(VIIa)

where X and X 'are anionic ligands; R1 and R2 independently denote a hydrogen atom, a C1-C6 alkyl group, a C5-C6 cycloalkyl group or a C5-C6 aryl group; R3 denotes a hydrogen atom, a C1-C6 alkyl group, a C5-C6 cycloalkyl group, a C5-C6 aryl group or a COR9 group, COOR9, CONHR9 or SO2R9 where R9 is a hydrogen atom, a C1-C6 alkyl group, a C5-C6 aryl or heteroaryl group optionally substituted with at least one substituent selected from C1-C6 alkoxy groups, C1-C6 alkyl pyridinium groups, NO2 group, CF3 group and halogen atoms; a, b and c independently denote a hydrogen atom or a C1-C6 alkyl group; Z represents a methylene or carbonyl group; and L is a neutral ligand of formula (VIII):

(VIII) in which:

the groups Ra independently designate a C5-C6 aryl group which is unsubstituted or substituted by one or more groups chosen from C1-C6 alkyl groups, C1-C6 alkoxy groups, halogen atoms and perhaloalkyl groups; C1-C6,

the Rb groups independently denote a hydrogen atom, a C1-C6 alkyl group, a halogen atom or a C5-C6 aryl group. and the compounds of formula (VIIIb):

(VIIb)

where X and X 'are anionic ligands; R4 denotes a hydrogen atom, a C1-C6 alkyl group, a C1-C6 perhaloalkyl group, an alkyl pyridinium group, a C1-C6 alkoxy group, a C5-C6 cycloalkyl group, a C5 aryl group; -C6 which is optionally substituted with at least one group selected from C1-C6 alkyl groups, halogen atoms and NO2 group; R5, R6, R7 and R8 independently denote a hydrogen atom, a C1-C6 alkyl group, a C5-C6 cycloalkyl group or a C5-C6 aryl group; and L is as defined above.

3. Method according to claim 2, characterized in that the anionic ligands are halogen atoms, preferably chlorine atoms. 4. Process according to claim 2 or 3, characterized in that Ra is selected from the group consisting of 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, 2,4,6-trimethylphenyl tris (trifluoromethyl) phenyl, from 2,

4,6-trichlorophenyl and hexafluorophenyl, preferably Ra is 2,6-diisopropylphenyl.

5. Process according to any one of claims 2 to 4, characterized in that, in the formula (VIIa), RI is a hydrogen atom; R2 is methyl, ethyl or isopropyl, preferably ethyl; R3 is a group -COOR9 where R9 is a C1-C6 alkyl group, preferably an isopropyl group; a, b and c denote a hydrogen atom; and Z is a carbonyl group.

6. Process according to any one of claims 2 to 4, characterized in that, in the formula (Vllb), R4 denotes a C1-C6 alkoxy group or a CF3 group, preferably a C1-C6 alkoxy group; R5, R7 and R8 each denote a hydrogen atom; R6 is a C1-C6 alkyl group, preferably an isopropyl group.

7. Method according to any one of claims 1 to 6, characterized in that the compound of formula (V) is predominantly of stereochemical configuration (E _x , Z _x + ₂ ), preferably it has a ratio (E / Z ) _x of at least 85:15, preferably of at least 90:10 or even at least 95: 5 and a ratio (Z / E) _x + ₂ of at least 80:20 or even at least 90: 10.

8. Process according to any one of Claims 1 to 7, characterized in that the compound of formula (V) corresponds to one of the following definitions:

• X = -OCOR where R = -CH3; A is an alkylene chain with n carbon atoms in which n is from 1 to 12, preferably from 2 to 8, more preferably n = 6; m is an integer ranging from 0 to 7, preferably from 1 to 4, more preferably m = 1.

X = -COOR with R is a C1-C6 alkyl group, preferably R = -CH3; A is an alkenylene chain with n carbon atoms in which n is from 1 to 12, preferably from 2 to 6, more preferably n = 2; m is an integer ranging from 0 to 7, preferably from 1 to 3, more preferably m = 2.

9. Process according to any one of claims 1 to 8, characterized in that the compound of formula (V) has the following definition: X = -OCOR where R denotes a C1-C6 alkyl group; A is an alkylene chain with n carbon atoms in which n is from 1 to 12, preferably from 5 to 10, more preferably n = 9; m is an integer ranging from 0 to 7, preferably from 1 to 3, more preferentially m = 2; and is converted by hydrolysis to a compound of formula (VI) where Y = OH.

10. Process according to any one of claims 1 to 8, characterized in that the compound of formula (V) has the following definition: X = -OCOR where R denotes a C1-C6 alkyl group; A is an alkylene chain with n carbon atoms in which n is from 1 to 12, preferably from 6 to 10, more preferably n = 7; m is an integer ranging from 0 to 7, preferably from 0 to 3, more preferably m = 2; and is converted by hydrolysis and then oxidation to a compound of formula (VI) where Y = oxo.