Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
  • C07F5/02—Boron compounds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
  • C07F7/02—Silicon compounds
  • C07F7/08—Compounds having one or more C—Si linkages
  • C07F7/0803—Compounds with Si-C or Si-Si linkages
  • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
  • B01J21/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
  • B01J21/066—Zirconium or hafnium; Oxides or hydroxides thereof
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
  • C07F5/02—Boron compounds
  • C07F5/025—Boronic and borinic acid compounds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07J—STEROIDS
  • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00

Definitions

• the present invention relates to a process for preparing alkenylaminoboranes and their derivatives, and their uses.
• Alkenylaminoboranes are compounds exhibiting both the peculiarities of alkenylboranes and aminoboranes.
• Alkenylboranes are versatile synthetic intermediates which find application in numerous organic synthesis strategies. They are in particular of great interest as synthesis intermediates, in particular in post-functionalization steps (halogenation, cross-coupling) allowing the introduction of chemical functions useful for obtaining natural or biological products. Vinyl units are indeed very present in many molecules of biological interest. The stereoselective synthesis of these compounds is in particular very important because it conditions the properties of the molecules.
• 1-Alkenylboronates can be obtained by hydroboration of terminal alkynes.
• the hydroboration reaction of terminal alkynes consists of the addition of a boron-hydrogen bond to the triple bond giving rise to the corresponding alkenylborane.
• the hydroboration of alkynes can be done without a catalyst but requires the use of specific boranes such as dialkoxyboranes, catecholborane or pinalcolborane.
• these reagents are expensive and / or unstable.
• Catecholborane for example, exhibits great instability in air and moisture and requires purification steps before use.
• the reaction with cathecholborane leads to by-products and the relative instability of the catechol alkenylboronates obtained necessitates an additional transformation into more stable boron esters.
• the stereoselectivity of uncatalyzed hydroboration is not general, a mixture of regioisomers can be obtained.
• the hydroboration of alkynes can be catalyzed by transition metals, or it can be carried out by heterogeneous catalysis or organocatalysis.
• the hydroboration of alkynes catalyzed by transition metals has mainly been studied with pinacolborane and catecholborane, expensive reagents.
• the hydroboration reaction is stereospecific and the formation of (E) isomers is favored.
• a method of obtaining alkenylboranes catalyzed by a transition metal is described in document (WO2006 / 132896), but it implements the addition of a dialkoxyborane and does not make it possible to obtain alkenylaminoborane.
• a method for obtaining known aminoboranes is that described in patent EP 1 458 729.
• the method described in this patent comprises the reaction between diisopropylaminoborane (DIPOB) of formula (iPr) 2 NBH 2 and a compound of formula AX, wherein A may be a vinyl group and X is a halogenated leaving group, in the presence of a palladium catalyst.
• DIPOB diisopropylaminoborane
• iPr formula
• AX is a halogenated leaving group
• One aspect of the present invention is a process for preparing alkenylaminoboranes by hydroboration of a terminal alkyne in the presence of an aminoborane and a specific catalyst.
• alkenylaminoborane as an intermediate compound for the preparation of various families of boron derivatives, such as alkenyldiaminoboranes, alkenyldialkoxyboranes or alkenylfluoroborates.
• Another aspect of the present invention is the use of alkenylaminoboranes and derivative families obtained from alkenylaminoboranes, as reaction intermediates for coupling or multistage syntheses.
• Another aspect of the present invention is the use of an alkenylaminoborane as an intermediate for the stereoselective preparation of bromoalkenes.
• the inventors have shown that it is possible to prepare alkenylaminoboranes by contacting a terminal alkyne and an aminoborane in the presence of a specific catalyst.
• alkenyl or alkynyl group of 2 to 18 carbon atoms linear or branched, optionally carrying at least one substituent
• aryl group of 2 to 12 carbon atoms where the aryl is chosen from the group of aromatics or heteroaromatics, optionally carrying at least one substituent
• alkyl aryl group an alkyl aryl group, where the aryl is chosen from the group of aromatics or heteroaromatics, optionally carrying at least one substituent,
• halogen chosen from F, Cl, Br, and I
• R a , R , R c and R d which may be identical or different, represent H, Cl, alkyl, alkenyl, linear or branched alkynyl, cycloalkyl, cycloalkenyl, aryl, in particular phenyl, or aromatic or non-aromatic heterocyclic groups of 1 to 18 carbon atoms, optionally bearing at least one substituent, where said substituents are chosen from:
• R 1 is a group chosen from isopropyl and cyclohexyl, n is an integer from 1 to 3, comprising the contacting, preferably in a single synthetic step: of a terminal alkyne, of the following formula: R having the meanings indicated above, of an aminoborane of formula BH 2 -N (R I ) 2, and of a catalyst chosen from: Schwartz's reagent (Cp 2 ZrHCl), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2), 9-borabicyclo (3.3.1) nonane (9-BBN).
• a catalyst chosen from: Schwartz's reagent (Cp 2 ZrHCl), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2), 9-borabicyclo (3.3.1) nonane (9-BBN).
• formula (I) it is understood that when n
• R is a C1 alkyl group, that is to say that R has a carbon atom: R is a -CH 3 group if n is equal to 1, R is a -CH 2 group - if n is equal to 2 and R is a -CH- group if n is equal to 3.
• R is a C2 alkynyl group
• R is a CHoC- group if n is equal to 1
• R is a -CoC- group if is equal to 2
• the valence n cannot be equal to 3 because the R group does not cannot carry three alkenylaminoborane functions.
• the alkenylaminoborane function can:
• R a cannot be H or Cl .
• the invention relates to a process for preparing an alkenylaminoborane of formula (I) in which n is equal to 1, R is a silyl group -SiR a R b R c, in particular R a , R b and R c, which are identical or different, are chosen from H, Cl atoms, alkyl groups with 1 to 18 carbon atoms or phenyls,
• Ri and R 2 are identical, and have the following formula (1-1-1):
• the aminoborane of formula BH 2 -N (R I ) 2 is preferably chosen from diisopropylaminoborane (DIPOB) and dicyclohexylaminoborane (DICOB).
• DIPOB diisopropylaminoborane
• DICOB dicyclohexylaminoborane
• the steric hindrance provided by the two isopropyl or cyclohexyl substituents prevents, by their arrangement and their volume, the approach of a reagent to the amine function.
• DIPOB and DICOB exhibit steric hindrance limiting access to the nitrogen atom, thus making the nitrogen atom not very reactive.
• These two aminoborans DIPOB and DICOB are in particular inexpensive.
• the specific catalysts used for the hydroboration of the alkyne by an aminoborane are chosen from Schwartz's reagent (Cp 2 ZrHCI), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2) and 9-borabicyclo (3.3.1) nonane (9-BBN). These molecules have the following structures:
• the process for forming alkenylaminoboranes of formula (I) according to the present invention can be carried out in a single synthesis step, ie a so-called one-pot procedure.
• the use of low-cost raw materials (alkyne, aminoboranes or amine-borane complexes) is advantageous in particular for carrying out the reaction on an industrial scale.
• the process for forming alkenylaminoboranes of formula (I) according to the present invention is stereospecific and forms isomers (E).
• the process is carried out in the absence of an additive to promote the stereoselectivity of the reaction.
• the method according to the invention advantageously makes it possible to dispense with the use in the medium of an additive such as an amine to promote stereoselectivity.
• the catalyst alone is capable of reacting the alkyne and the borane to form only (E) isomers.
• the process is performed in the absence of a base.
• the method according to the invention advantageously makes it possible to dispense with the use in the medium of an additional base which can promote the formation of uncontrolled secondary products.
• the catalyst alone is capable of reacting the alkyne and the borane.
• the process according to the invention does not require the addition of a base such as triethylamine (Et 3 N), unlike reactions using a transition metal complex as catalyst.
• n is equal to 1, 2 or 3, preferably n is equal to 1.
• the invention relates to a process for preparing an alkenylaminoborane of formula (I), in which the process is carried out at a temperature ranging from 20 ° C to 80 ° C, preferably at 70 ° C. .
• reaction temperature When the reaction temperature is higher than room temperature, the reaction is carried out with an amount of catalyst less than that used for a reaction carried out at room temperature.
• ambient temperature is meant temperatures of 10 ° C to 40 ° C, in particular of the order of 20 ° C to 30 ° C.
• reaction temperature is above 80 ° C.
• impurities such as boron-free alkenes obtained from photodeborylation.
• the invention relates to a process for preparing an alkenylaminoborane of formula (I), in which the catalyst is the Schwartz reagent of formula (C 5 H 5 ) 2 ZrHCl or Cp 2 ZrHCl. In one embodiment, the invention relates to a process for preparing an alkenylaminoborane of formula (I), in which the catalyst is used in an amount ranging from 0.5% to 20%, in particular from 1% to 12% , preferably 12%. The amounts are expressed as a molar percentage relative to the limiting reagent.
• the process is carried out in less than 24 hours, preferably in less than an hour.
• the process according to the invention is carried out in a solvent, in particular an aprotic solvent, preferably chosen from N, N-Dimethylformamide (DMF), tetrahydrofuran (THF), methylterbutylether (MTBE) , diethylether (Et 2 0), benzene, toluene, xylene, dioxane, or mixtures thereof, in particular MTBE or THF.
• a solvent in particular an aprotic solvent, preferably chosen from N, N-Dimethylformamide (DMF), tetrahydrofuran (THF), methylterbutylether (MTBE) , diethylether (Et 2 0), benzene, toluene, xylene, dioxane, or mixtures thereof, in particular MTBE or THF.
• aprotic solvent preferably chosen from N, N-Dimethylformamide (DMF), tetrahydrofuran (THF),
• MTBE and THF with a respective boiling point of 66 ° C and 55 ° C used as solvent in the process of the invention, make it possible to isolate alkenylaminoboranes of formula (I) having a boiling point greater than 70 ° C by proceeding by evaporation of the solvent, for example using a rotary evaporator.
• the invention relates to a process in which the degree of conversion of the alkyne to alkenylaminoborane is greater than 80%, preferably greater than 97%.
• the yield of the process for preparing the alkenylaminoborane of formula (I) according to the invention is quantitative.
• conversion rate is understood to mean the level of terminal alkyne which has reacted during the process. This level can be determined by analyzing the final product obtained by 1 H NMR. The comparison of the signal of the propargyl proton, on which the hydroboration reaction is carried out, with that of the other protons of the alkyne serving as a reference, makes it possible to evaluate the quantity of alkyne having reacted during the process according to the invention .
• the alkenylaminoborane of formula (I) obtained according to the process of the invention does not require an additional purification step because the purity of the product obtained is greater than 90%, in particular greater than 91%, 92% , 93%, 94%, 95%, 96%, 97%, 98% or 99%.
• the alkenylaminoborane is obtained with a purity allowing other reactions to be carried out directly in the same reaction medium in order to obtain other families of boron derivatives.
• the alkenylaminoborane of formula (I) can be isolated by simple filtration of the reaction medium through kielselghur or through diatomaceous earth, preferably over Celite®, using an eluent.
• the term "purification step” means any step subsequent to the synthesis step making it possible to increase the purity of the product.
• a purification step mention may be made of liquid chromatography, high performance liquid chromatography, recrystallization or distillation.
• the step of filtering the mixture for example over kielselghur or diatomaceous earth, and evaporating the solvent.
• the alkenylaminoborane of formula (I) can be isolated in the form of a liquid or a solid with a product purity greater than 90%, in particular greater than 91%, 92%, 93%, 94%, 95%, 96%. , 97%, 98% or 99%.
• the aminoborane used in the process of the invention can be obtained commercially or synthetically. It can also be generated from an amine-borane complex during the hydroboration reaction.
• the invention relates to a process for preparing an alkenylaminoborane of formula (I) in which the aminoborane of formula BH 2 -N (R I ) 2 is formed in situ by a dehydrogenation reaction of 'an amine-borane complex of formula H 3 B ⁇ - NH (R I ) 2 , preferably during a single synthesis step.
• the dehydrogenation reaction of the amine-borane H 3 B ⁇ - NH (R I ) 2 is carried out using an organomagnesium agent.
• amine-borane complex of formula H 3 B ⁇ - NH (R I ) 2 is understood to mean a compound comprising a BH 3 group in which the vacant p orbital is filled by the pair of electrons of an amine NH (R I ) 2 .
• DIPAB diisopropylamine-borane
• DICAB dicyclohexylamine-borane
• the term “formed in situ” is understood to mean the fact that the aminoborane is formed directly during the implementation of the process by mixing the amine-borane complex and an organomagnesium agent, for example, during the reaction of hydroborylation.
• the process of the invention can thus be carried out in a single simultaneous step of formation of the aminoborane and of hydroborylation of the alkyne.
• an organomagnesium agent is used for the in situ generation of the aminoborane from the amine-borane complex and is a Grignard reagent, preferably PhMgBr or CH 3 MgBr.
• Amine-borane complexes are known for their stability towards water, air and light. They are relatively simple to produce and can be stored over the long term. It is thus possible to select amine-borane complexes, some of which are more chemically stable and / or commercially available than their aminoborane counterparts.
• the object of the process is the preparation of an alkenylaminoborane of formula (I), in which formula (I) corresponds to one of the following structures:
• Another object of the invention is the use of a terminal alkyne, of diisopropylaminoborane (DIPOB) or of dicyclohexylaminoborane (DICOB) and of a catalyst chosen from Schwartz's reagent (Cp 2 ZrHCI), dicyclohexylborane (HBCy) , diisopinocamphenylborane (HBipc2), 9-borabicyclo (3.3.1) nonane (9-BBN), for the implementation of a process for preparing an alkenylaminoborane of formula (I) according to the invention.
• DIPOB diisopropylaminoborane
• DIOB dicyclohexylaminoborane
• a catalyst chosen from Schwartz's reagent (Cp 2 ZrHCI
• Another object of the invention is the use of diisopropylaminoborane (DIPOB) or dicyclohexylaminoborane (DICOB) for carrying out a process for preparing an alkenylaminoborane of formula (I) according to the invention.
• DIPOB diisopropylaminoborane
• DIOB dicyclohexylaminoborane
• Another object of the invention is the use of a catalyst chosen from Schwartz's reagent (Cp 2 ZrHCI), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2), 9-borabicyclo (3.3.1) nonane ( 9-BBN), for the implementation of a process for preparing an alkenylaminoborane of formula (I) according to the invention.
• a catalyst chosen from Schwartz's reagent (Cp 2 ZrHCI), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2), 9-borabicyclo (3.3.1) nonane ( 9-BBN), for the implementation of a process for preparing an alkenylaminoborane of formula (I) according to the invention.
• Another subject of the invention is the use of Schwartz's reagent (Cp 2 ZrHCl), for the implementation of a process for preparing an alkenylaminoborane of formula (I) according to the invention.
• a reaction mechanism is proposed according to the scheme below for a process for preparing an alkenylaminoborane of formula (I) using DIPOB and Schwartz's reagent.
• a step of hydrozirconation of the alkyne by the reagent of Schwartz takes place. It is followed by the addition of the DIPOB. The addition is made with retention of configuration.
• the zirconium diisopropylaminoborohydride thus formed can then release a hydride in the medium to form the alkenylaminoborane of formula (I).
• the hydride is immediately captured by the positively charged zirconium derivative.
• the Schwartz reagent is thus regenerated and the catalytic cycle is initiated.
• the invention also relates to the use of an alkenylaminoborane of formula (I) prepared according to the process of the invention for the preparation of one of the compounds of following formulas (II), (III) or (IV): in which R and n have the meanings indicated above, R 2 , R 3 , R 4 , and R 5 , are identical or different and represent hydrogens, alkyl groups, alkenyls, linear or branched alkynyls, cycloalkyls, cycloalkenyls, aryls, or aromatic or non-aromatic heterocyclics, from 1 to 18 carbon atoms, optionally carrying at least one substituent, where said substituents are chosen from alkyl groups of 1 to 18 carbon atoms, linear, branched or cyclic, and halogens F, Cl, Br and I, where R 2 and R 3 can be linked together to form a ring.
• Another object of the present invention relates to a process for preparing an alkenyldiaminoborane compound of formula (II): in which
• R and n have the meanings indicated above,
• R 2 , R 3 , R 4 , and R 5 have the meanings indicated above, comprising the following steps: a) a step of preparing an alkenylaminoborane of formula (I) according to the invention, b) a step of alcoholysis by an alcohol R'-OH of the alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula ( lM):
• (lM) in particular the alcohol R'-OH is chosen from MeOH, EtOH, PrOH or iPrOH, c) a step of substitution of the R'O alkoxyl groups of the compound of formula (lM) by an amino group comprising the groups R 2 , R 3 , R 4 and R 5 where R 2 , R 3 , R 4 , and R 5 have the meanings indicated above, making it possible to obtain the compound of formula (II), d) optionally a purification step .
• steps a), b) and c) are carried out in one-pot.
• the alcohol used in alcoholysis step b) is methanol.
• the alcoholysis is advantageously carried out using 3 equivalents of alcohol molecule per alkenylaminoborane function.
• the methanolysis is carried out at low temperature (-40 ° C) by adding to the reaction medium 3 equivalents of methanol molecule per alkenylaminoborane function.
• the amino group is a diamine containing the groups R 2 , R 3 , R 4 and R 5.
• the amino group is advantageously bidentate and the groups R 2 and R 3 are linked together to form a ring.
• the invention relates to a process for preparing alkenyldiaminoborane compounds of formula (II), wherein said amino group is diaminonaphthalene of following formula:
• step c) of substitution of the alkoxyl groups with diaminonaphthalene (dan) is carried out in the presence of FeCl 3 and imidazole in a mixture of MeCN: H 2 0 (1: 1) solvents at temperature (AT) for 4 hours.
• Another object of the present invention relates to a process for preparing an alkenylboronate compound of formula (III): in which
• R and n have the meanings indicated above,
• R 2 and R 3 have the meanings indicated above, comprising the following steps: a) a step of preparing an alkenylaminoborane of formula (I) according to the invention; b) a step of alcoholysis with an alcohol R'-OH of the alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula (1M):
• (1M) in particular the alcohol is chosen from MeOH, EtOH, PrOH or iPrOH; c) a stage of substitution of the R'O alkoxyl groups of the compound of formula (1M) by an alcohol or diol comprising groups R 2 and R 3 , in particular by a transesterification reaction; d) optionally a purification step; preferably steps a), b) and c) are carried out in one-pot.
• the alcohol used in alcoholysis step b) is methanol.
• the alcoholysis is advantageously carried out using 3 equivalents of alcohol molecule per alkenylaminoborane function.
• a diol containing the R 2 , R 3 groups is used during substitution step c) .
• the diol group is advantageously bidentate and the R 2 and R 3 groups are linked together to form a ring.
• the substitution of the alkoxyl groups is carried out by a transesterification reaction.
• the transesterification is carried out by adding to the reaction medium the alcohol or the diol in diethyl ether at -40 ° C. and the solution is brought from -40 ° C. to room temperature.
• the invention relates to a process for preparing an alkenylboronate compound of formula (III), in which said diol used is pinacol or neopentylgycol.
• the process for preparing an alkenylboronate compound of formula (III), in which said diol used is pinacol or neopentylgycol does not require a step of purification of the final product.
• Another subject of the invention relates to a process for preparing an alkenylfluoroborate compound of formula (IV): in which
• R and n have the meanings indicated above, comprising the following steps: a) a step of preparing an alkenylaminoborane of formula (I) according to the invention; b) a step of alcoholysis with an alcohol R'-OH of the alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula (1M):
• (1M) in particular the alcohol R'-OH is chosen from MeOH, EtOH, PrOH or iPrOH; b) a stage of substitution of the R'O alkoxyl groups of the compound of formula (1M) by a fluorinated group, in particular carried out by bringing into contact with KHF 2 ; d) optionally a purification step; preferably steps a), b) and c) are carried out in one-pot.
• the alcohol used in alcoholysis step b) is methanol.
• the alcoholysis is advantageously carried out using 3 equivalents of alcohol molecule per alkenylaminoborane function.
• step c) of transformation of the intermediate alkenylboronate of formula (1M) into potassium trifluoroborate salt by substitution of the alkoxyl groups is carried out by adding to the reaction medium a solution of KHF 2 prepared in methanol at -40 ° C and the mixture is brought from -40 ° C to room temperature (AT).
• the object of the process is the preparation of one of the compounds of formulas (II), (III) or (IV), corresponding to one of the following structures: eo where Bdan represents i where Bpin represents: where Bneo represents i
• Another subject of the invention is the use of the compounds of formulas (I), (II), (III) or (IV) prepared according to one of the processes of the invention, as reaction intermediate compounds, in particular for the implementation of stereoselective, multistage or coupling syntheses, in particular for SuzukhMiyaura, Chan-Lam, Petasis and halogenation reactions.
• Another object of the invention is the use of the process according to the invention for carrying out the preparation of the compounds of formulas (I), (II), (III) or (IV), as reaction intermediate compounds , in particular for the implementation of stereoselective, multistage or coupling syntheses, in particular for Suzuki-Miyaura, Chan-Lam, Petasis and halogenation reactions.
• the invention also relates to the use of an alkenylaminoborane of formula (I) for carrying out a stereoselective synthesis of bromoalkenes (Z) or (E).
• the invention also relates to the use of an alkenylaminoborane of formula (I) prepared according to the process of the invention for the implementation of a stereoselective synthesis of bromoalkenes (Z) or (E ).
• Another object of the present invention relates to a process for the stereoselective preparation of the bromoalkenes (Z) or (E) of the following formulas: in which R and n have the meanings indicated above, comprising the following steps: a) a step of alcoholysis with an alcohol R'-OH of an alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula (1M) :
• (1M) R'OH being in particular chosen from MeOH, EtOH, PrOH or iPrOH; b) a step of bromination of the intermediate alkenylboronate of formula (1M) in the presence of CuBr 2 , in order to obtain mainly the bromoalkene (E); c) optionally a step of purification of the bromoalkene (E) obtained, preferably on silica gel; to obtain mainly the isomer (E); or else: a) a step of adding dibroma Br 2 to an alkenylaminoborane of formula (I) to form an anti-addition of Br 2 to the alkene function of alkenylaminoborane and lead to a dibromoalkane via a bromonium bromonium, b) a step of anti-elimination of the aminoborane function and of a bromide of said dibromoalkane, preferably by adding a strong alkoxide base (R ”
• “predominantly” means an isomer level (isomer yield) greater than or equal to 50%, preferably greater than or equal to 70%, even more preferably greater than or equal to 90%.
• Another object of the present invention relates to a process for the stereoselective preparation of the bromoalkenes (Z) or (E) of the following formulas: in which R and n have the meanings indicated above, comprising the following steps: a) a step of preparing an alkenylaminoborane of formula (I) according to the invention; b) a step of alcoholysis with an alcohol R'-OH of the alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula (1M):
• steps a), b) and c) are carried out in one-pot for the two sequences.
• the alcoholysis step leading to the alkenylboronate of formula (1M) is carried out by adding 3 equivalents of methanol molecule per alkenylaminoborane function and carrying the reaction medium at -78 ° C for one hour.
• the step of bromination by electrophilic trapping of the alkenylboronate of formula (1M) is carried out by adding CuBr 2 in a THF: H 2 0 mixture. (1: 1) and bringing the reaction medium to 70 ° C for 16 hours.
• the step of adding anti Br 2 to the alkene function, forming the dibromoalkane via a bromonium bromonium is carried out by introducing the dibromium Br 2 in solution in MTBE at 0 ° C and maintaining the reaction medium at 0 ° C for one hour.
• the anti elimination step is carried out by adding MeONa at 0 ° C and maintaining the reaction medium at 0 ° C for 2 hours.
• the invention also relates to the use of an alkenylaminoborane of formula (I) prepared according to the process of the invention for carrying out a stereoselective synthesis of haloalkenes.
• the invention also relates to the use of an alkenylaminoborane of formula (I) prepared according to the process of the invention for carrying out a stereoselective synthesis of alkenes.
• alkenylaminoboranes of formula (I) are prepared according to the following scheme:
• the conversion relates to the disappearance of the alkyne.
• the conversion rate is determined using the 1 H NMR signals by comparison between the signals of the protons of the alkyne not brought into play during the reaction which serve as a reference and the signal of the propargyl proton.
• a total conversion of 100% corresponds to the total disappearance of the quantity of starting alkyne introduced, indicating that all the alkynes have been transformed during the process.
• the alkenyldiaminoboranes are prepared according to the following scheme:
• the alkenylaminoborane of formula (I) is prepared according to Example 1 then:
• the intermediate is subjected to a substitution of the methoxyl groups by diaminonaphthalene (dan) in the presence of FeCl 3 and imidazole in a mixture of MeCN: H 2 0 solvents (1: 1) at room temperature (AT) for 4h.
• methanolysis (3 equiv.) Is carried out at low temperature (-40 ° C), for 1 h, to form the intermediate methyl alkenylboronate; 2. the intermediate is transesterified by adding a solution of pinacol in diethyl ether at -40 ° C, the solution being brought from -40 ° C to room temperature (AT), for 4 h: the methoxyl groups are substituted by pinacol (pine).
• a methanolysis (3 equiv.) Is carried out at low temperature (-40 ° C), for 1 h, in order to form the intermediate methyl alkenylboronate; 2.the intermediate is transesterified to allow the substitution of the methoxyl groups by neopentylglycol (neo): the neopentylglycol is added in solution in diethyl ether at -40 ° C and the solution is brought from -40 ° C to room temperature (TA), for 4 hours. Tests have been carried out with several terminal alkynes exhibiting different R groups. The results of the conversion rate of the alkynes and the yield after washing of the products without a purification step are reported in Table 4.
• a methanolysis (3 equiv.) Is carried out at low temperature (-40 ° C), for 1 h, in order to form the intermediate methyl alkenylboronate; 2. the intermediate methyl alkenylboronate is converted into a potassium trifluoroborate salt by substitution of the methoxyl groups, in the presence of a solution of KHF 2 prepared in methanol at -40 ° C; the solution is brought from -40 ° C. to ambient temperature (AT) for 4 h.

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