Process for preparing α,β-unsaturated carbonyl compounds

Abstract

The present invention relates to the field of organic synthesis, and more particularly to a method for the oxidation of allylic alcohols to α,β-unsaturated carbonyl compounds in the presence of a zirconium catalyst and a hydrogen acceptor.

Description

[Technical Field]

[0001] The present invention relates to the field of organic synthesis, and more particularly to a method for the oxidation of allylic alcohols to α,β-unsaturated carbonyl compounds in the presence of a zirconium catalyst and a hydrogen acceptor.

[0002] Background technology α,β-Unsaturated carbonyl compounds represent highly desirable scaffolds that can be used as such or as key intermediates to prepare more complex compounds in various fields, such as perfumery, cosmetics, pharmaceuticals, or agricultural chemistry, among others. In particular, carvone or (E)-4-methyldec-3-en-5-one is a valuable compound known as a fragrance component or can be an important intermediate for more complex compounds. One approach to α,β-unsaturated carbonyl compounds is the oxidation of the corresponding alcohol, specifically the Oppenauer oxidation, which can be easily implemented on an industrial scale. Nevertheless, such oxidations are carried out at high temperatures. Furthermore, since the Oppenauer reaction is reversible, the hydrogen acceptor is added incrementally, and then the formed alcohol and unreacted hydrogen acceptor are removed after each increment. However, there is a need to develop sustainable methods that reduce energy consumption and simplify method implementation.

[0003] The present invention allows for the oxidation of allyl alcohols to α,β-unsaturated carbonyl compounds under catalytic conditions and at lower temperatures, while providing complete conversion and maintaining high yields. To our knowledge, the use of zirconium catalysts in such oxidation processes has not been reported in the prior art.

[0004] Summary of the Invention The present invention relates to a novel process that allows the preparation of α,β-unsaturated carbonyl compounds under mild conditions not reported or suggested in the prior art, which process makes it possible to suppress the sequential addition of hydrogen acceptors and multiple distillations along the process.

[0005] Therefore, a first object of the present invention is a method for oxidizing allyl alcohol to an α,β-unsaturated carbonyl compound, said method comprising: i) Formula [Zr(L)(X) r ](I) or [Zr(L') p (X) n ](I') wherein L is a bisphenolate, triphenolate, or calixarene having at least four phenolic units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least four phenolic units; ii) a hydrogen acceptor; and

[0006] The second object of the present invention is to i) Formula [Zr(L)(X) r ](I) or [Zr(L') p (X) n ](I') wherein L is a bisphenolate, triphenolate, or calixarene having at least four phenolic units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least four phenolic units; ii) a hydrogen acceptor; and

[0007] MODE FOR CARRYING OUT THE INVENTION Surprisingly, it has now been discovered that the oxidation of allylic alcohols to α,β-unsaturated carbonyl compounds can be carried out in an advantageous manner using a catalyst represented by formula (I) or (I') and a hydrogen acceptor. These unprecedented conditions allow for the production of α,β-unsaturated carbonyl compounds in very high yields without the need for high temperatures, sequential addition of hydrogen acceptors, and removal of the formed alcohol by distillation before each addition of the hydrogen acceptor. The method of the present invention provides simple access to α,β-unsaturated carbonyl compounds.

[0008] Therefore, a first object of the present invention is a method for oxidizing allyl alcohol to an α,β-unsaturated carbonyl compound, said method comprising: iii) Formula [Zr(L)(X) r ](I) or [Zr(L') p (X) n ](I') wherein L is a bisphenolate, triphenolate, or calixarene having at least four phenolic units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least four phenolic units; iv) a hydrogen acceptor; and

[0009] The term "α,β-unsaturated carbonyl compound" is understood as an enal or enone compound.

[0010] According to an optional embodiment of the present invention, p is 1 and n is 3. In other words, the catalyst of formula (I') is a compound of formula [Zr(L')(X)3](I”) wherein L' and X have the same meaning as defined above.

[0011] According to any embodiment of the present invention, the phenolate has the formula [ka] wherein the wavy line indicates the position of the bond between the zirconium atom and L, q is an integer between 0 and 3, and R 1 simultaneously or independently represent at least one substituent of the aromatic ring, and are selected from the group consisting of a halogen atom, a cyano group, a nitro group, and C optionally substituted with one or more halogen atoms. 1-6 Alkyl group, C 1-6 an alkoxy group or a COOR group, where R is a hydrogen atom or a C 1-6 is an alkyl group, represented by the formula:

[0012] The term "optionally" is understood to mean that a group may or may not include certain functional groups or substituents. The term "one or more" is understood to include 1 to 7, preferably 1 to 5, and more preferably 1 to 3 functional groups.

[0013] The terms "alkyl group," "alkenyl group," or "alkoxy group" are understood to include straight-chain or branched alkyl, alkenyl, or alkoxy groups. The terms "alkanediyl group" or "alkenediyl group" are understood to include straight-chain, branched, alicyclic, or cyclic alkanediyl or alkenediyl groups. The terms "alkenyl," "alkenediyl," and "cycloalkenyl" are understood to include one, two, or three olefinic double bonds, preferably one or two olefinic double bonds, and even more preferably one double bond. The term "cycloalkenyl" is understood to include monocyclic or fused, spiro, and / or bridged bicyclic or tricyclic cycloalkenyl groups, preferably monocyclic cycloalkenyl groups.

[0014] According to any embodiment of the present invention, R 1is a halogen atom, a cyano group, a nitro group, C 1-4 an alkoxy group, optionally substituted with 1 to 3 halogen atoms; 1-4 alkyl group, or R is a hydrogen atom or C 1-4 It may be a COOR group, which is an alkyl group. In particular, R 1 is a chlorine atom, a fluorine atom, a cyano group, a nitro group, C 1-3 an alkoxy group or a C optionally substituted with 1 to 3 halogen atoms; 1-3 R may be an alkyl group or a COOR group, and R is a hydrogen atom or a C 1-3 It is an alkyl group. In particular, R 1 is a cyano group, a nitro group, a COOH group, or a C optionally substituted with 1 to 3 fluorine atoms. 1-3 More particularly, R 1 can be a cyano group, a nitro group, or a methyl group optionally substituted with 1 to 3 fluorine atoms.

[0015] According to any embodiment of the invention, q may be 0 or 1, in particular 1.

[0016] According to any embodiment of the present invention, R 1 may be an ortho substituent on the aromatic ring relative to the 1-position. In other words, the phenolate of formula (I) is [ka] where the wavy line indicates the position of the bond between the zirconium atom and L, and R 1’ is a hydrogen atom or R as defined above 1 is a group represented by the formula:

[0017] According to any embodiment of the present invention, the phenolate is selected from the group consisting of 2-nitrophenolate, ortho-cresolate, 2-(trifluoromethyl)phenolate, and 2-cyanophenolate.

[0018] According to any embodiment of the present invention, the bisphenolate has the formula [ka] wherein the wavy line indicates the position of the bond between the zirconium atom and L, m is 0 or 1, and R 2 , R 3 , R 4 , R 5 , R 2’ , R 3’ , R 4’ , and R 5’ When considered independently and separately, they are hydrogen, halogen atoms, nitro groups, 2H-benzo[d][1,2,3]triazol-2-yl groups, C 1-6 Alkoxy group, C 1-6 a thioalkyl group, or optionally a halogen atom, a hydroxy group, an amine group, or C 1-3 C substituted with one or more alkoxy groups 1-10 is an alkyl group, or R 2 and R 3 , or R 3 and R 4 , or R 2’ and R 3’ , or R 3’ and R 4’ When considered together, -O-(CH2) y represents an —O— group, where y is 1 or 2, or a C aryl group, C 5-6 forming a cycloalkyl group, each of which optionally contains a halogen atom, a hydroxy group, or C 1-3 Z is an oxygen or sulfur atom, a (—CH—) group, a —NH— group, a —SO— group, a —SS— group, a —CH—NH—CH— group, or a —C(R 6 )(R 7 )-group, wherein R 6 and R 7 are each independently considered as a hydrogen atom or a C6 aryl group, a C6 heteroaryl group or a C 1-3 alkyl groups, each of which optionally contains 1 to 3 halogen atoms or C 1-3and the heteroatom is one or more of an oxygen atom or a nitrogen atom.

[0019] According to any embodiment of the present invention, R 2 , R 3 , R 4 , R 5 , R 2’ , R 3’ , R 4’ , and R 5’ When considered separately, they are independently hydrogen atoms, chlorine atoms, or C 1-9 can be an alkyl group, or R 2 and R 3 , or R 3 and R 4 , or R 2’ and R 3’ , or R 3’ and R 4’ when taken together form a C6 aryl group.

[0020] According to any embodiment of the present invention, R 2 and R 2’ are, independently of each other, a hydrogen atom or C 1-4 In particular, R 2 and R 2’ may be, independently of one another, a hydrogen atom or a methyl or tert-butyl group. In particular, R 2 and R 2’ may be a hydrogen atom or a tert-butyl group. More particularly, R 2 and R 2’ can be a tert-butyl group.

[0021] According to any embodiment of the present invention, R 3 and R 3’ are, independently of each other, a hydrogen atom or C 1-4 In particular, R 3 and R 3’ are, independently of each other, a hydrogen atom or C 1-3 In particular, R 3 and R3’ are, independently of each other, a hydrogen atom or C 1-2 In particular, R 3 may be, independently of one another, a hydrogen atom or a methyl group. More particularly, R 3 and R 3’ can be a hydrogen atom.

[0022] According to any embodiment of the present invention, R 4 and R 4’ are, independently of each other, a hydrogen atom or C 1-9 In particular, R 4 and R 4’ is a hydrogen atom or C 1-4 In particular, R 4 and R 4’ may be, independently of one another, a hydrogen atom or a methyl or tert-butyl group. More particularly, R 4 and R 4’ can be a methyl group or a tert-butyl group.

[0023] According to any embodiment of the present invention, R 5 and R 5’ are, independently of each other, a hydrogen atom or C 1-4 In particular, R 5 and R 5’ are, independently of each other, a hydrogen atom or C 1-3 In particular, R 5 and R 5’ are, independently of each other, a hydrogen atom or C 1-2 In particular, R 5 may be, independently of one another, a hydrogen atom or a methyl group. More particularly, R 5 and R 5’ can be a hydrogen atom.

[0024] According to any embodiment of the present invention, R 3 and R 4 may, when taken together, form a C6 aryl group.

[0025] According to any embodiment of the present invention, R 3’ and R 4’ may, when taken together, form a C6 aryl group.

[0026] According to an optional embodiment of the present invention, m is 1.

[0027] According to an optional embodiment of the present invention, Z is CR 6 R 7 It is the base.

[0028] According to any embodiment of the present invention, R 6 and R 7 When considered separately, they are independently hydrogen atoms or C 1-2 In particular, R 6 and R 7 When considered separately, R may independently represent a hydrogen atom or a methyl group. 6 can be a hydrogen atom, and R 7 can be a hydrogen atom or a methyl group.

[0029] According to any embodiment of the present invention, the bisphenolate may be selected from the group consisting of [1,1′-biphenyl]-2,2′-diol, [1,1′-binaphthalene]-2,2′-diol, 6,6′-methylenebis(2,4-di-tert-butylphenol), 6,6′-(ethane-1,1-diyl)bis(2,4-di-tert-butylphenol), 6,6′-methylenebis(2-(tert-butyl)-4-methylphenol), 6,6′-oxybis(2-(tert-butyl)-4-methylphenol), and 6,6′-thiobis(2-(tert-butyl)-4-methylphenol).

[0030] According to any embodiment of the present invention, the triphenolate has the formula [ka] wherein the wavy line indicates the position of the bond between the zirconium atom and L, and Z, m, R2 , R 3 , R 4 , R 5 , R 2’ , R 3’ , R 4’ , and R 5’ has the same meaning as defined above, and R 2” , R 3” , R 4” , and R 5” are R 2 , R 3 , R 4 , R 5 is a group represented by the formula:

[0031] According to any embodiment of the present invention, the triphenolate is 2,6-bis[(2-hydroxyphenyl)methyl]phenol, 2,6-bis[(2-hydroxy-3,5-dimethylphenyl)methyl]-4-methylphenol, 2,6-bis(3-tert-butyl-5-methyl-2-hydroxybenzyl)-4-methylphenol, 4-chloro-2,6-bis[(2-hydroxy-5-methylphenyl)methyl]phenol, 2,6-bis[(5-chloro-2-hydroxyphenyl)methyl]-4-methylphenol, 2,6-bis[(2-hydroxy-4-methylphenyl)methyl]phenol,

[0033] The hydroxyphenyl ester may be selected from the group consisting of (2S)-1-[3,5-bis[[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-oxobutyl)phenyl]methyl]-2,4,6-trihydroxyphenyl]-2-methyl-1-butanone, 2,2'-methylenebis[6-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol].

[0032] According to any embodiment of the present invention, the calixarene may contain 4, 6, or 8 phenolic units, in particular 4 phenolic units. Calixarene with 4 phenolic units has the formula [ka] wherein the wavy line indicates the position of the bond between the zirconium atom and L, and Z, m, R 3 , R 4 , and R 5 is represented by the formula, which has the same meaning as defined above.

[0033] According to any embodiment of the present invention, the calixarene having at least four phenolic units may be selected from the group consisting of p-tert-butylcalix[4]arene, 25,26,27,28-tetrahydroxycalix[4]arene, Calix[6]arene, tert-butylcalix[8]arene, tert-butylcalix[6]arene, Calix[8]arene, and p-isopropylcalix[4]arene.

[0034] According to any embodiment of the present invention, the anionic ligands may be, independently of one another, halogen atoms, β-diketonates, OOCR 8 group or OR 9 is a group, wherein R 8 C 1-10 alkyl group, benzyl group, naphthyl group, or phenyl group optionally substituted with a hydroxy group; R 9 C 1-6 The term "β-diketonate" refers to a C(═O)—CH═C(O - ) group. In particular, β-diketonates are understood to be ligands containing the formula R 10 -C(=O)-CH=C(O - )-R 11 wherein R 10 and R 11 are independent of each other, C 1-6 Alkyl groups, especially C 1-4The alkyl group is preferably a methyl group, a propyl group, an isopropyl group, or a tert-butyl group. Non-limiting examples of β-diketonates include 4-oxopent-2-en-2-olate, 2,2-dimethyl-5-oxohex-3-en-3-olate, 2,6-dimethyl-5-oxohept-3-en-3-olate, or 2,2,6,6-tetramethyl-5-oxohept-3-en-3-olate. In particular, R 8 is C 1-8 Alkyl groups, especially C 1-6 Alkyl groups, more particularly C 1-5 In particular, R 9 is C 1-4 It may be an alkyl group, in particular a propyl, isopropyl, butyl or tertbutyl group. In particular, the anionic ligand is selected from the group consisting of acetylacetonate, acetate and pivalate.

[0035] According to a particular embodiment, when p is 0 and n is 4, X is a group of formula OR as defined above. 9 It is an alkoxide represented by the formula:

[0036] According to an optional embodiment of the present invention, the catalyst is represented by formula (I):

[0037] According to an optional embodiment of the present invention, r is 2 and L is a bisphenolate.

[0038] According to an optional embodiment of the present invention, the catalyst represented by formula (I) may be selected from the group consisting of zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), zirconium, [2,2'-methylenebis[(4-6-di-tert-butyl)phenolate]]bis(2,4-pentanedionate), zirconium, [2,2'-methylenebis[(4-6-dimethyl)phenolate]]bis(2,4-pentanedionate), zirconium, [2,2'-ethylidenebis[(4-6-di-tert-butyl)phenolate]]bis(2,4-pentanedionate), and zirconium. The bis(2,4-pentanedionate) may be selected from the group consisting of zirconium, [2,2'-thiobis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), zirconium, [2,2'-oxobis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), zirconium, [[2,2'-binaphthalene]-1,1'-diolate]bis(2,4-pentanedionate), zirconium, [[2,2'-binaphthalene]-1,1'-diolate]bis(propanalate), and zirconium, [[2,2'-biphenyl]-1,1'-diolate]bis(propanalate).

[0039] The catalyst represented by formula (I) or (I') can be added to the reaction medium of the process of the present invention to form α,β-unsaturated carbonyl compounds in a wide range of concentrations. As a non-limiting example, values ​​of the catalyst concentration can range from 0.1 mol% to 10 mol% relative to the total amount of allyl alcohol. In particular, the catalyst concentration can be between 0.5 mol% and 5 mol%. It goes without saying that the process also works with a larger amount of catalyst. However, the optimal catalyst concentration depends on the nature of the catalyst, the nature of the allyl alcohol, the temperature, and the desired reaction time, as known to those skilled in the art.

[0040] Catalysts of formula (I) or (I') can be prepared by several methods, starting, for example, from Zr(acac)4 or Zr(OPr)4. Alternatively, catalysts of formula (I) or (I') can be formed in situ by reaction of Zr(OPr)4, phenol or bisphenol, and acetylacetone.

[0041] According to any one of the above embodiments of the present invention, the hydrogen acceptor is a hydrocarbon containing at least one carbonyl functional group and having a boiling point of 80° C. or higher, preferably 110° C. or higher, and even more preferably 120° C. or higher. The hydrogen acceptor reacts with the produced hydrogen to produce an alcohol. The hydrogen acceptor can be an aldehyde or a ketone. In particular, the hydrogen borrowing source is a hydrocarbon of the formula [ka] wherein R a is C optionally substituted with a hydroxy group or an aryl group 1-10 C linear alkyl groups, optionally substituted with hydroxy or aryl groups 2-10 C linear alkenyl group, optionally substituted with hydroxy or aryl groups 3-10 a branched or cyclic alkyl or alkenyl group, or optionally 1 to 5 C 1-3 represents a phenyl group, a hydroxy group, or a halogen atom substituted with an alkyl group or an alkoxy group, and R b is a hydrogen atom or R a represents a group, or R a and R b When taken together, they represent C optionally substituted with a hydroxy or aryl group. 2-10 The hydrogen acceptor represented by formula (II) is represented by the formula C 4-10 It is a compound.

[0042] The terms "aryl group" and "heteroaryl group" have their usual meaning in the art, i.e., an aromatic hydrocarbon group such as an optionally substituted phenyl group, pyridine group, or naphthyl group. Non-limiting examples of optional substituents on aryl groups include C 1-3 Mention may be made of alkyl or alkoxy groups, hydroxy groups or halogen atoms.

[0043] According to any one of the above embodiments, R a is a phenyl group, C 1-10 Straight chain alkyl group, or C 3-10 It may represent a branched or cyclic alkyl group, each optionally substituted with a hydroxy group. Preferably, R a represents a phenyl group, optionally substituted with a hydroxy group, 1-10 A straight chain alkyl group or a C optionally substituted with a hydroxy group 3-10 It may represent a branched or cyclic alkyl group. Preferably, R a is C optionally substituted with a hydroxy group 3-8 It may represent a linear or branched alkyl group. Even more preferably, R a may represent a phenyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyloctyl group.

[0044] According to any one of the above embodiments, R b represents a hydrogen atom or a C optionally substituted with a hydroxy group or an aryl group. 1-10 A straight chain alkyl group or a C optionally substituted with a hydroxy group or an aryl group 3-10 It may represent a branched or cyclic alkyl group. Preferably, R b may represent a hydrogen atom, a methyl group, an ethyl group, or a propyl group.

[0045] According to any one of the above embodiments, R a and R b When taken together, they represent C optionally substituted with a hydroxy group. 4-8It may represent a straight-chain branched alkanediyl or alkenediyl. Preferably, R a and R b When taken together, they represent C optionally substituted with a hydroxy group. 4-7 It may represent a straight-chain branched alkanediyl or alkenediyl. Preferably, R a and R b When considered together, C 4-7 Even more preferably, R a Yobi R b When considered together, C 4-5 It may represent a straight-chain alkanediyl.

[0046] Non-limiting examples of suitable hydrogen acceptors may include compounds selected from the group consisting of benzaldehyde, cyclohexanone, 2-heptanone, 2-octanone, 2-pentanone, acetophenone, 4-methyl-2-pentanone, isophorone, 3-methyl-2-butanone, and mixtures thereof.

[0047] The hydrogen acceptor can be added to the reaction medium of the method of the present invention to form the α,β-unsaturated carbonyl compound over a wide range of concentrations. Non-limiting examples of hydrogen acceptor concentrations include values ​​ranging from 1 to 5 equivalents, or even 1 to 2 equivalents, relative to the amount of allyl alcohol. It goes without saying that the method also works with more hydrogen acceptors. However, the optimal concentration of hydrogen acceptor depends on the nature of the catalyst, the nature of the allyl alcohol, the temperature, and the desired reaction time, as known to those skilled in the art.

[0048] According to any one of the above embodiments, the allyl alcohol is represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof; In the formula, R c is a hydrogen atom or C 1-10 Alkyl group or C 2-10 is an alkenyl group, Rd is a hydrogen atom or C 1-3 is an alkyl group, and R e is a hydrogen atom or C 1-5 is an alkyl group, and R f is a hydrogen atom or a methyl group, or R c and R e are considered as a whole, and C 2-16 Alkanediyl group or C 3-16 represents an alkenediyl group, or R d and R e are considered as a whole, and C 2-16 represents an alkanediyl group, or R c and R d are considered as a whole, and C 2-16 Alkanediyl group or C 3-16 The α,β-unsaturated carbonyl compound is a compound represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof, wherein R c , R d , and R e is a compound represented by the formula:

[0049] According to any one of the above embodiments, R f is a hydrogen atom.

[0050] According to any one of the above embodiments, the allyl alcohol is represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof; In the formula, R c is a hydrogen atom or C 1-10 Alkyl group or C 2-10 is an alkenyl group, R d is a hydrogen atom or C 1-3 is an alkyl group, and Re is a hydrogen atom or C 1-5 is an alkyl group, or R c and R e are considered as a whole, and C 2-16 Alkanediyl group or C 3-16 represents an alkenediyl group, or R d and R e are considered as a whole, and C 2-16 represents an alkanediyl group, or R c and R d are considered as a whole, and C 2-16 Alkanediyl group or C 3-16 The α,β-unsaturated carbonyl compound is a compound represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof, wherein R c , R d , and R e is a compound represented by the formula:

[0051] According to any one of the above embodiments, the allyl alcohol is represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof; In the formula, R c is C 1-10 is an alkyl group, and R d is a hydrogen atom or C 1-3 is an alkyl group, and R e is C 1-3 is an alkyl group, or R c and R e are considered as a whole, and C 2-16 represents an alkanediyl group, or R d and R e are considered as a whole, and C 2-16 represents an alkanediyl group, or Rc and R d are considered as a whole, and C 2-16 The α,β-unsaturated carbonyl compound is a compound represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof, wherein R c , R d , and R e is a compound represented by the formula:

[0052] The term "alkanediyl group" or "alkenediyl group" is understood to include linear, branched, cyclic, or alicyclic alkanediyl or alkenediyl groups.

[0053] For clarity, the phrase "any one of its stereoisomers or a mixture thereof" or similar phrases has the usual meaning as understood by a person skilled in the art, i.e., the compounds referred to in this invention may be pure enantiomers or mixtures of enantiomers. In other words, the compounds referred to in this invention may have at least one stereocenter that can have two different stereochemistries (e.g., R or S), e.g., R c The group may contain at least one stereocenter. The compound may be in the form of a pure enantiomer or a mixture of enantiomers. If the compound has two or more stereocenters, the compound referred to in the present invention may be in the form of a pure diastereoisomer or even a mixture of diastereoisomers. The compound may be racemic or scalemic. Thus, the compound may be a stereoisomer or a composition of matter containing or consisting of various stereoisomers.

[0054] The wavy line indicates that the double bond may be in the form of its E or Z isomer or a mixture thereof. For example, the present invention includes compositions of matter consisting of one or more compounds of formula (III) or one or more compounds of formula (IV) having the same chemical structure but differing in the configuration of the double bond.

[0055] According to any one of the above embodiments, R c is a hydrogen atom or C 1-8 Alkyl group or C 2-8 In particular, R c is a hydrogen atom or C 1-6 Alkyl group or C 2-6 In particular, R c is a hydrogen atom or C 1-4 Alkyl group or C 4-6 In particular, R c is a hydrogen atom or C 1-3 Alkyl group or C 4-6 In particular, R c is a hydrogen atom or C 1-3 Alkyl group or C 4-6 In particular, R c is a hydrogen atom or C 1-2 It can be an alkyl group or a C6 alkenyl group. More particularly, R c can be a hydrogen atom or methyl, ethyl, hex-3-en-1-yl or 4-methylpent-3-en-1-yl.

[0056] According to any one of the above embodiments, R e is a hydrogen atom or C 1-5 In particular, R e is a hydrogen atom, C 1-3 It may be an alkyl group or a pentyl group. In particular, R e can be a hydrogen atom or a methyl, ethyl or pentyl group. In particular, R e may be a hydrogen atom or a pentyl group. More particularly, R e can be a hydrogen atom or a straight chain pentyl group.

[0057] According to any one of the above embodiments, R d is a hydrogen atom or C 1-2 In particular, R d may be a hydrogen atom or a methyl group. More particularly, R d can be a methyl group.

[0058] According to any one of the above embodiments, R c and R d are considered as a whole, and C 2-12 Alkanediyl group or C 3-12 Represents an alkenediyl group. In particular, R c and R d are considered as a whole, and C 2-10 Alkanediyl group or C 3-10 Represents an alkenediyl group. In particular, R c and R d are considered as a whole, and C 2-8 Alkanediyl group or C 3-8 Represents an alkenediyl group. In particular, R c and R d are considered as a whole, and C 4-8 Alkanediyl group or C 4-8 Represents an alkenediyl group. In particular, R c and R d are considered as a whole, and C 6-8 Alkanediyl group or C 6-8 Represents an alkenediyl group. In particular, R c and R d are considered as one entity, and C is 1-4 C substituted with alkyl or alkenyl groups 5-6 Forms a cycloalkenyl. More particularly, R c and R d are taken together and represent 2-isopropenyl-1,4-butanediyl or the formula (a) [ka] and in the form of any one of its stereoisomers or a mixture thereof.

[0059] According to any one of the above embodiments, R d and R e are considered as a whole, and C 2-12 Represents an alkanediyl group. In particular, R d and R e are considered as a whole, and C 2-10 Represents an alkanediyl group. In particular, R d and R e are considered as a whole, and C 2-8 Represents an alkanediyl group. In particular, R d and R e are considered as a whole, and C 4-8 Represents an alkanediyl group. In particular, R d and R e are considered as a whole, and C 6-8 represents an alkanediyl group. More particularly, R d and R e are considered together and the equation (a) [ka] and in the form of any one of its stereoisomers or a mixture thereof.

[0060] According to any one of the above embodiments, R c and R e are considered as a whole, and C 2-12 Alkanediyl or C 3-12 Represents an alkenediyl group. In particular, R c and R e is considered as one, C 2-10 Alkanediyl group or C 3-10 Represents an alkenediyl group. In particular, R c and R e are considered as a whole, and C 2-8 Alkanediyl group or C 3-8 Represents an alkenediyl group. In particular, R c and Re are considered as a whole, and C 4-8 Alkanediyl group or C 4-8 Represents an alkenediyl group. In particular, R c and R e are considered as a whole, and C 5-8 Alkanediyl group or C 5-8 Represents an alkenediyl group. In particular, R c and R e are considered as a whole, and C 5-7 Alkanediyl group or C 5-7 Represents an alkenediyl group. In particular, R c and R e taken together represent a C6 alkanediyl group or a C6 alkenediyl group. More particularly, R c and R e are considered together and include a 2-isopropenyl-1,3-propanediyl group, a group represented by formula (b) or a group represented by formula (c) [ka] and in the form of any one of these stereoisomers or a mixture thereof.

[0061] According to any one of the above embodiments, R c and R e are considered as a whole, and C 2-12 represents an alkanediyl group, and R d is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R c and R e are considered as a whole, and C 2-8 represents an alkanediyl group, and R d is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R c and R e are considered as a whole, and C 2-6 represents an alkanediyl group, and R d is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R c and R e are considered as a whole, and C2-4 represents an alkanediyl group, and R d is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R c and R e are considered as a whole, and C 2-4 represents an alkanediyl group, and R d is a hydrogen atom or C 1-2 It is an alkyl group. In particular, R c and R e are considered as a whole, and C 2-3 represents an alkanediyl group, and R d is a hydrogen atom or C 1-2 More particularly, R c and R e are considered together and represent a C3 alkanediyl group, and R d is a methyl group.

[0062] According to any one of the above embodiments of the present invention, the allyl alcohol is selected from the group consisting of carveol, (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol, 4-methyl-3-decen-5-ol, 6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-ol, i.e. pinocarveol, (4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)methanol, 1-octen-3-ol, 4,7,7 trimethylbicyclo[4.1.0]hept-4-en-3-ol, The most common allylic alcohols are 3,7,7-trimethylbicyclo[4.1.0]hept-3-en-2-ol, geraniol, nerol, 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol, (2E,6Z)-nona-2,6-dien-1-ol, 3-methyl-2-buten-1-ol, 6-isopropyl-3-methylcyclohex-2-en-1-ol, 5-isopropyl-2-methylcyclohex-2-en-1-ol, and (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol.

[0063] According to any one of the above embodiments of the present invention, the α,β-unsaturated carbonyl compound is selected from the group consisting of carvone, 6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbaldehyde, 4-methyldec-3-en-5-one, 6,6-dimethyl-2-methylidenebicyclo[3.1.1]heptan-3-one, 4-prop-1-en-2-ylcyclohexene-1-carbaldehyde, 1-octen-3-one, 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-one, 3,7,7 -trimethylbicyclo[4.1.0]hept-3-en-2-one, (2E)-3,7-dimethylocta-2,6-dienal, (2Z)-3,7-dimethylocta-2,6-dienal, 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one, (2E,6Z)-nona-2,6-dienal, 5-isopropyl-2-methylcyclohex-2-en-1-one, 6-isopropyl-3-methylcyclohex-2-en-1-one, or 3-methyl-2-butenal. In particular, the α,β-unsaturated carbonyl compound is carvone.

[0064] According to any one of the embodiments of the present invention, the inventive process for oxidizing allyl alcohol to α,β-unsaturated carbonyl compounds is carried out at a temperature comprised between 50° C. and 190° C. In particular, the temperature ranges between 100° C. and 140° C. Of course, the skilled person will also be able to select the preferred temperature as a function of the melting and boiling points of the starting and final products and the desired time of the reaction or conversion.

[0065] The process of the present invention for the oxidation of allylic alcohols to α,β-unsaturated carbonyl compounds can be carried out in the presence or absence of a solvent. If a solvent is required or used for practical reasons, any solvent conventional for the purposes of the present invention can be used in such reaction types. Non-limiting examples include C 2 olefins such as xylene, toluene, 1,3-diisopropylbenzene, cumene or pseudocumene. 6-12Examples include aromatic solvents or mixtures thereof, hydrocarbon solvents such as cyclohexane, heptane, etc., nitrile solvents such as acetonitrile, ester solvents such as ethyl acetate, or ether solvents such as tetrahydrofuran, diethyl ether, methyltetrahydrofuran, etc., or mixtures thereof. The choice of solvent is a function of the nature of the substrate and / or catalyst, and those skilled in the art are fully capable of selecting the most suitable solvent in each case to optimize the reaction.

[0066] The process of the present invention for the oxidation of allyl alcohol to A,B-unsaturated carbonyl compounds can be carried out under batch or continuous conditions.

[0067] The process of the present invention for the oxidation of allyl alcohol to an α,β-unsaturated carbonyl compound can be carried out under atmospheric pressure.

[0068] According to any one of the above embodiments, the allylic alcohol can be prepared by rearrangement of an epoxide to the allylic alcohol. In other words, the method of the present invention comprises: i) rearrangement of epoxides to allylic alcohols, and ii) oxidation of the allylic alcohol obtained in step i) to an α,β-unsaturated carbonyl compound as defined above.

[0069] According to a specific embodiment of the present invention, the rearrangement of the epoxide to an allylic alcohol and the oxidation of the allylic alcohol to an α,β-unsaturated carbonyl compound can be carried out in one pot. The term "one pot" means that both steps are carried out consecutively in a single reaction system. In this case, the hydrogen acceptor and the zirconium catalyst are added after the first step is completed. The zirconium catalyst may also be generated in situ after the first step is completed.

[0070] According to a particular embodiment of the present invention, the rearrangement of the epoxide to the allylic alcohol is carried out in the presence of a catalyst of formula Zn(aa)2, where aa is an α-aminocarboxylate or β-aminocarboxylate having at least 3 carbon atoms, or a catalyst of formula Zn(carboxylate)2, and an aminophenol.

[0071] According to any one of the above embodiments, the α-amino acid is selected from the group consisting of proline, valine, lysine, D-proline, D-valine, D-lysine L-proline, L-valine, L-lysine, 2-phenylglycine, phenylalanine, 2-amino-2-methylpropanoic acid, and mixtures thereof, and the aminophenol is selected from the group consisting of 2-aminophenol, 2-aminomethylphenol, and mixtures thereof.

[0072] According to any embodiment of the present invention, the β-aminocarboxylate is an anthralinate.

[0073] According to any one of the above embodiments, the catalyst represented by the formula Zn(carboxylate)2 is selected from the group consisting of Zn(2-ethylhexenoate)2, Zn(OAc)2, Zn(benzoate)2, Zn(naphthenate)2, Zn(laurate)2, Zn(stearate)2, Zn(palmitate)2, Zn(2-octyldodecanoate)2, and the aminophenol is selected from the group consisting of 2-aminophenol, 2-aminomethylphenol, and mixtures thereof.

[0074] According to any one of the above embodiments, the epoxide may be represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof, wherein R c , R d , and R e is a compound of the formula: with the same meaning as defined above.

[0075] According to any one of the above embodiments, the epoxide may be represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof, wherein R c , R d , and R e is a compound represented by the formula:

[0076] According to any one of the above embodiments of the present invention, non-limiting examples of epoxides include 1,2-limonene oxide, 3,8,8-trimethyl-4-oxatricyclo[5.1.0.0 3,5 ]octane, 4,8,8 trimethyltricyclo[5.1.0.0 2,4 ]octane, 2-isopropyl-5-methyl-7-oxabicyclo[4.1.0]heptane, 4-isopropyl-1-methyl-7-oxabicyclo[4.1.0]heptane, α-pinene oxide, β-pinene oxide, 2,2,6-trimethyl-1-oxaspiro[2.5]oct-5-ene, 2,2,6-trimethylspiro[2.5]oct-4-ene, and caryophyllene oxide. In particular, the epoxide may be 1,2-limonene oxide.

[0077] The catalyst of formula Zn(aa)2 or Zn(carboxylate)2 can be added to the reaction medium of the process of the present invention to form allyl alcohol in a wide range of concentrations. By way of non-limiting example, values ​​of the catalyst concentration can range from 0.1 mol% to 10 mol% relative to the total amount of epoxide. In particular, the catalyst concentration can be between 0.25 mol% and 5 mol%. It goes without saying that the process also works with higher amounts of catalyst. However, the optimal catalyst concentration depends, as known by those skilled in the art, on the nature of the catalyst, the nature of the epoxide, the temperature, and the desired reaction time.

[0078] According to any embodiment of the present invention, the aminophenol is selected from the group consisting of 2-aminophenol, 2-aminomethylphenol, 2-amino-4-chlorophenol, 2-amino-3-methylphenol, 2-amino-5-chlorophenol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 2-amino-3-nitrophenol, 2-amino-4-methoxyphenol, 2-amino-4-tertbutylphenol, and mixtures thereof.

[0079] The aminophenol can be added to the reaction medium of the process of the present invention to form allyl alcohol in a wide range of concentrations. Non-limiting examples of aminophenol concentration values ​​include values ​​ranging from 0.1 mol% to 20 mol%, or even 0.5 mol% to 5 mol%, relative to the amount of epoxide. It goes without saying that the process also works with higher amounts of aminophenol. However, the optimal concentration of aminophenol depends on the nature of the aminophenol, the nature of the epoxide, the nature of the catalyst, the temperature, and the desired reaction time, as known to those skilled in the art.

[0080] According to any one of the embodiments of the present invention, the inventive process for the rearrangement of epoxides to allylic alcohols is carried out at a temperature comprised between 50°C and 190°C. In particular, the temperature is in the range between 100°C and 190°C. In particular, the temperature is in the range between 100°C and 185°C. In particular, the temperature is in the range between 160°C and 190°C. More particularly, the temperature is in the range between 170°C and 190°C. Of course, the skilled person will also be able to select the preferred temperature as a function of the melting and boiling points of the starting and final products and the desired time of the reaction or conversion.

[0081] The process of the present invention for the rearrangement of epoxides to allylic alcohols can be carried out in the presence or absence of a solvent. If a solvent is required or used for practical reasons, any solvent conventional for the purposes of the present invention can be used in such reaction types. Non-limiting examples include C 2 alkane, such as xylene, toluene, 1,3-diisopropylbenzene, cumene or pseudocumene, or mixtures thereof. 6-12 Examples include hydrocarbon solvents such as aromatic solvents, cyclohexane, heptane, or mixtures thereof. The choice of solvent is a function of the nature of the substrate and / or catalyst, and those skilled in the art are fully capable of selecting the most suitable solvent in each case to optimize the reaction.

[0082] The process of the present invention for the rearrangement of an epoxide to an allylic alcohol can be carried out under batch or continuous conditions.

[0083] The process of the present invention for the rearrangement of an epoxide to an allylic alcohol can be carried out under atmospheric pressure.

[0084] Another object of the present invention is to provide i) Formula [Zr(L)(X) r ](I) or [Zr(L') p (X) n ](I') wherein L is a bisphenolate, triphenolate, or calixarene having at least four phenolic units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least four phenolic units; ii) a hydrogen acceptor; and

[0085] According to any embodiment of the present invention, the catalytic system as defined above is suitable for use in a process for the oxidation of allyl alcohol to an α,β-unsaturated carbonyl compound as defined above.

[0086] Another object of the present invention is to provide a process for the oxidation of allyl alcohols to α,β-unsaturated carbonyl compounds, comprising the steps of: i) Formula [Zr(L)(X) r ](I) or [Zr(L') p (X) n ](I') wherein L is a bisphenolate, triphenolate, or calixarene having at least four phenolic units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least four phenolic units; ii) the use of a catalyst system comprising or consisting of a hydrogen acceptor;

[0087] Typical modes for carrying out the method of the invention are reported below in the Examples.

[0088] Example The invention will now be described in further detail by the following examples, in which abbreviations have their usual meaning in the art and temperatures are given in degrees Celsius (°C). Preparation of pre-catalyst and ligand solutions was carried out under an inert atmosphere (argon) using standard Schlenk techniques. Solvents were dried by conventional procedures and distilled under an argon atmosphere. NMR spectra were recorded at 20°C on a Bruker AV300, AV400, or AV500 MHz spectrometer. Chemical shifts were recorded relative to the solvent signals (chloroform, δ H =7.26 ppm,δ CSignal assignments are reported in ppm relative to the ion concentration (=77.0 ppm). 1 H, 1 H-COSY, -NOESY, 13 C. 1 H-HSQC and HMBC experiments were recorded to ensure that the NMR of all compounds prepared conforms to the NMR reported in the literature.

[0089] Example 1 Catalytic oxidation of carveol using complexes [Zr(L)(acac)2] or [Zr(L')(acac)3] (acac = acetylacetonate) A mixture of carveol (Aldrich, approximately 1:1 isomer mixture), [Zr(L)(acac)2] or [Zr(L')(acac)3] (1 mol%), and cyclohexanone (1.5 equiv.) was heated to 130°C in a glass reactor equipped with a stirrer, thermometer, and condenser. The reaction mixture was heated at 130°C for 4 hours to complete the conversion of carveol to carvone. Results using various L or L' ligands from Table 2 are shown in Table 1.

[0090] [Table 1]

[0091] [Table 2]

[0092] Example 2 Preparation of R-(-)-carvone via one-pot sequential rearrangement of R-(+)-1,2-limonene oxide using Zn(L-prolinate)2 as catalyst, and Oppenauer oxidation of R-(-)-carveol in the presence of zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and cyclohexanone as hydrogen acceptor. A mixture of R-(+)-1,2-limonene oxide (R-LMO), Zn(L-prolinate)2 (0.25 mol%), and 2-aminophenol (4 equiv. / Zn) was heated at 185 °C for 9 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. Upon completion of the rearrangement process, the reaction mixture was cooled to room temperature. 1 mol% zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and 1.1 equiv. of cyclohexanone relative to the initial R-LMO were added. The reaction mixture was heated at 130 °C for 4 h to complete the conversion of carveol to carvone. Distillation afforded carvone in 99% yield based on the intermediate carveol title and 82% yield based on the initial R-LMO. This material was purified using conventional methods to give R-(-)-carvone with a purity of >99GC%.

[0093] Example 3 Preparation of R-(-)-carvone via one-pot sequential rearrangement of R-(+)-1,2-limonene oxide using Zn(L-prolinate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol in the presence of zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and benzaldehyde as a hydrogen acceptor. A mixture of R-(+)-1,2-limonene oxide (R-LMO), Zn(L-prolinate)2 (0.25 mol%), and 2-aminophenol (4 equiv. / Zn) was heated at 185 °C for 9 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. Upon completion of the rearrangement process, the reaction mixture was cooled to room temperature. 1 mol% zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and 1.1 equiv. of benzaldehyde (relative to the initial R-LMO) were added. The reaction mixture was heated at 130 °C for 4 h to complete the conversion of carveol to carvone. Distillation afforded carvone in 96% yield based on the intermediate carveol title and 79% yield based on the initial R-LMO. This material was purified using conventional methods to give R-(-)-carvone with a purity of >99GC%.

[0094] Example 4 Preparation of R-(-)-carvone via one-pot sequential rearrangement of R-(+)-1,2-limonene oxide using Zn(L-prolinate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol in the presence of zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and benzaldehyde as a hydrogen acceptor. A mixture of R-(+)-1,2-limonene oxide (R-LMO), Zn(L-prolinate)2 (0.25 mol%), and 2-aminophenol (4 equiv. / Zn) was heated at 185 °C for 9 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. Upon completion of the rearrangement process, the reaction mixture was cooled to room temperature. 1 mol% zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and 1.1 equiv. of benzaldehyde (relative to the initial R-LMO) were added. The reaction mixture was heated at 100 °C for 2 h and then at 130 °C for an additional 2 h to complete the conversion of carveol to carvone. Distillation afforded carvone in 99% yield based on the intermediate carveol title and 82% yield based on the initial R-LMO. This material was purified using conventional methods to give >99 GC% R-(-)-carvone.

[0095] Example 5 Preparation of R-(-)-carvone via one-pot sequential rearrangement of R-(+)-1,2-limonene oxide using Zn(2-ethylhexanoate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol in the presence of zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and benzaldehyde as a hydrogen acceptor. A mixture of R-(+)-1,2-limonene oxide (R-LMO), Zn(2-ethylhexanoate)2 (0.5 mol%), and 2-aminophenol (3 equiv. / Zn) was heated at 185 °C for 15 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. Upon completion of the rearrangement process, the reaction mixture was cooled to room temperature. 1 mol% zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and 1.1 equiv. of benzaldehyde (relative to the initial R-LMO) were added. The reaction mixture was heated at 100 °C for 2 h and then at 130 °C for an additional 2 h to complete the conversion of carveol to carvone. Distillation afforded carvone in 99% yield based on the intermediate carveol title and 83% yield based on the initial R-LMO. This material was purified using conventional methods to give R-(-)-carvone with a purity of >99GC%.

[0096] Example 6 Preparation of R-(-)-carvone via one-pot sequential rearrangement of R-(+)-1,2-limonene oxide using Zn(2-ethylhexanoate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol in the presence of zirconium, in situ generated [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate), and benzaldehyde as a hydrogen acceptor. A mixture of R-(+)-1,2-limonene oxide (R-LMO), Zn(2-ethylhexanoate)2 (0.5 mol%), and 2-aminophenol (3 equiv. / Zn) was heated at 185°C for 15 hours in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. Upon completion of the rearrangement process, the reaction mixture was cooled to 30°C. 1 mol% of Zr(OPr)4 (70% in propanol), 6,6'-methylenebis(2-(tert-butyl)-4-methylphenol), and 2.2 equiv. of acetylacetone were added, and the reaction mixture was stirred for 1 hour. Then, 1.1 equiv. of benzaldehyde (relative to the initial R-LMO) was added. The reaction mixture was heated at 100°C for 2 hours and then at 130°C for an additional 2 hours to complete the conversion of carveol to carvone. Distillation afforded carvone in 99% yield based on the intermediate carveol title and 83% yield based on the initial R-LMO. This material was purified using conventional methods to yield R-(-)-carvone in greater than 99 GC% purity.

[0097] Example 7 Catalytic oxidation of (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol using the conditions of the present invention A mixture of (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol (10 g, 65.7 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, resulting in a 79% conversion. After distillation of the residue, the expected product, i.e., 6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbaldehyde, was obtained in 91% yield.

[0098] Example 8 Catalytic oxidation of (E)-4-methyldec-3-en-5-ol using the conditions of the present invention A mixture of (E)-4-methyldec-3-en-5-ol (5 g, 29 ml, 4 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, resulting in 92% conversion. After distillation of the residue, the corresponding ketone, (E)-4-methyldec-3-en-5-one, was obtained in 98% yield.

[0099] Example 9 Catalytic oxidation of 6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-ol using the conditions of the present invention A mixture of 2 g of 6,6-dimethyl-2-methylidenebicyclo[3.1.1]heptan-3-ol, 13.1 mmol of zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and 1.1 equiv. of benzaldehyde was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, resulting in 82% conversion. After distillation of the residue, 6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-one was obtained in 91% yield.

[0100] Example 10 Catalytic oxidation of (4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)methanol using the conditions of the present invention A mixture of (4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)methanol (4 g, 25.9 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, resulting in 80% conversion. After distillation of the residue, 4-(prop-1-en-2-yl)cyclohex-1-ene-1-carbaldehyde was obtained in 95% yield.

[0101] Example 11 Catalytic oxidation of 1-octen-3-ol using the conditions of the present invention A mixture of 1-octen-3-ol (4 g, 31 g, 2 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser at 130 °C for 2 h, resulting in 38% conversion. After distillation of the residue, 1-octen-3-one was obtained in 97% yield.

[0102] Example 12 Catalytic oxidation of 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol using the conditions of the present invention A mixture of 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol (2 g, 13 g, 1 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, giving 82% conversion and 70% selectivity to 7,7-trimethylbicyclo[4.1.0]hept-4-en-3-one.

[0103] Example 13 Catalytic oxidation of geraniol using the conditions of the present invention A mixture of geraniol (4 g, 25.9 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, giving 68% conversion and 87% selectivity to (2E)-3,7-dimethylocta-2,6-dienal.

[0104] Example 14 Catalytic oxidation of nerol using the conditions of the present invention A mixture of nerol (4 g, 25.9 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol %), and benzaldehyde (1.1 equiv.) was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, giving 58% conversion and 85% selectivity to (2Z)-3,7-dimethylocta-2,6-dienal.

[0105] Example 15 Catalytic oxidation of 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol using the conditions of the present invention A mixture of 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol (5 g, 32.8 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated at 130 °C for 2 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, giving 99% conversion and 98% selectivity to 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one.

[0106] Example 16 Catalytic oxidation of (2E,6Z)-nona-2,6-dien-1-ol using the conditions of the present invention A mixture of (2E,6Z)-nona-2,6-dien-1-ol (4 g, 28.5 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol%), and benzaldehyde (1.1 equiv.) was heated at 130°C for 2 hours in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, giving 65% conversion and 90% selectivity to (2E,6Z)-nona-2,6-dienal.

[0107] Example 17 Catalytic oxidation of 3-methyl-2-buten-1-ol using the conditions of the present invention A mixture of 3-methyl-2-buten-1-ol, i.e., prenol (4 g, 46, 4 mmol), zirconium, [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolate]]bis(2,4-pentanedionate) (1 mol.%), and benzaldehyde (1.1 equivalents) was heated at 130°C for 2 hours in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser, resulting in 45% conversion and 95% selectivity to 3-methyl-2-butenal, i.e., prenal.

[0108] Example 18 Preparation of R-(-)-carvone via one-pot sequential rearrangement of R-(+)-1,2-limonene oxide and Oppenauer oxidation of R-(-)-carveol under present and comparative conditions A mixture of 1,2-limonene oxide (60% cis isomer and 40% trans isomer, 400 g), catalyst, and 2-aminophenol (2-AP) (the equivalent amount of 2-AP relative to Zn is specified in Table 3) was heated to the temperature specified in Table 3 in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. The temperature was maintained until the R-LMO conversion exceeded 96%. After cooling, the oxidation catalyst was added along with the hydrogen acceptor (amount specified in Table 3). In some cases, the excess hydrogen acceptor (HA) and its corresponding alcohol were selectively removed, followed by sequential addition of the hydrogen acceptor. For clarity, when 2 / 2 is reported in the time column, this means that half of the total amount of HA was added initially, heated at the reported temperature for 2 hours, and then the unreacted HA along with its corresponding alcohol was removed by distillation, and the operation was then repeated. For example, 2 / 2 / 2 means that HA was added three times, with 2-hour intervals. The crude carvone was then purified by distillation to obtain carvone with a purity of >98%. The yields are reported in the Carvone Isolated Yield column. Separately or together, the excess of HA and its corresponding alcohol were also distilled. Their overall yields ((mol HA excess + mol alcohol) / mol initial total HA) are also reported when possible.

[0109] Table 3: Rearrangement of 1,2-limonene oxide to carveol followed by oxidation and Oppenauer oxidation to give R-(-)-carvone in one pot using inventive and comparative conditions. [Table 3] 1) Conditions as reported in WO 2003004448 2) Conditions as reported in WO 2021151790 3) Conditions as reported in WO 2003004448, but excluding the temperature of oxidation 4) Conditions of the present invention 5) 2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol] 6) 1,2-Limonene oxide

[0110] In contrast to prior art conditions, the present conditions allow for the isolation of carvone in high yields with very efficient recovery of the hydrogen acceptor or the corresponding alcohol. When the hydrogen acceptor is benzaldehyde, the reduction product formed is benzyl alcohol, a valuable component that can be used as a fragrance ingredient.

Claims

1. 1. A process for oxidizing allyl alcohol to an α,β-unsaturated carbonyl compound, said process comprising: i) Formula [Zr(L)(X) ｒ ] (I) or [Zr(L') ｐ (X) ｎ ](I′) wherein L is a bisphenolate, triphenolate, or calixarene having at least four phenolic units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least four phenolic units; ii) a hydrogen acceptor; and

2. The phenolate has the formula 【Chemistry 1】 where the wavy line indicates the position of the bond between the zirconium atom and L, and R １’ represents a hydrogen atom, a halogen atom, a cyano group, a nitro group, C １－６ an alkoxy group, optionally substituted with one or more halogen atoms; １－６ an alkyl group or a COOR group, where R is a hydrogen atom or a C １－６ The method of claim 1 , wherein the alkyl group is an alkyl group.

3. 3. The method of claim 2, wherein the phenolate is selected from the group consisting of 2-nitrophenolate, ortho-cresolate, 2-(trifluoromethyl)phenolate, and 2-cyanophenolate.

4. The bisphenolate has the formula 【Chemistry 2】 where the wavy line indicates the position of the bond between the zirconium atom and L, m is 0 or 1, and R ２ , R ３ , R ４ , R ５ , R ２’ , R ３’ , R ４’ , and R ５’ When considered independently and separately, they represent hydrogen, a halogen atom, a nitro group, a 2H-benzo[d][1,2,3]triazol-2-yl group, C １－６ Alkoxy group, C １－６ a thioalkyl group, or optionally a halogen atom, a hydroxy group, an amine group, or C １－３ C optionally substituted with one or more alkoxy groups １－１０ alkyl group or R ２ and R ３ , or R ３ and R ４ , or R ２’ and R ３’ , or R ３’ and R ４’ When considered together, -O-(CH ２ ) ｙ represents an —O— group, where y is 1 or 2, or C ６ Aryl group, C ５－６ cycloalkyl groups, each of which is optionally substituted with a halogen atom, a hydroxy group, or C １－３ Z is an oxygen atom or a sulfur atom, (-CH ２ -) ２ group, -NH- group, -SO ２ - group, -S-S- group, -CH ２ -NH-CH ２ - group, or -C(R ６ ) (R ７ )-group, wherein R ６ and R ７ are hydrogen atoms or C when considered independently and separately. ６ Aryl group, C ６ Heteroaryl group or C １－３ alkyl groups, each of which optionally contains 1 to 3 halogen atoms or C １－３ The method of claim 1, wherein the heteroatom is one or more of an oxygen atom or a nitrogen atom, and the heteroatom is optionally substituted with an alkoxy group.

5. 5. The method of claim 4, wherein the bisphenolate is selected from the group consisting of [1,1'-biphenyl]-2,2'-diol, [1,1'-binaphthalene]-2,2'-diol, 6,6'-methylenebis(2,4-di-tert-butylphenol), 6,6'-(ethane-1,1-diyl)bis(2,4-di-tert-butylphenol), 6,6'-methylenebis(2-(tert-butyl)-4-methylphenol), 6,6'-oxybis(2-(tert-butyl)-4-methylphenol), and 6,6'-thiobis(2-(tert-butyl)-4-methylphenol).

6. The anionic ligands are each independently selected from the group consisting of a halogen atom, a β-diketonate, an OOCR ８ group or OR ９ is a group, wherein R ８ is C １－１０ alkyl group, benzyl group, naphthyl group, or phenyl group optionally substituted with a hydroxy group; R ９ is C １－６ The method of any one of claims 1 to 5, wherein the group is an alkyl group.

7. 7. The method according to any one of claims 1 to 6, wherein the hydrogen acceptor is a hydrocarbon containing at least one carbonyl functional group and having a boiling point of 80°C or higher, preferably above 120°C.

8. 8. The method of any one of claims 1 to 7, wherein the hydrogen acceptor is selected from the group consisting of benzaldehyde, cyclohexanone, octalinone, 2-heptanone, 2-octanone, 2-pentanone, acetophenone, 4-methyl-2-pentanone, 3-methyl-2-butanone, isophorone, and mixtures thereof.

9. 9. The method according to any one of claims 1 to 8, wherein the allyl alcohol is carveol and the α,β-unsaturated carbonyl compound is carvone.

10. The method comprises: i) rearrangement of epoxides to allylic alcohols, and ii) oxidation of the allyl alcohol obtained in step i) to the α,β-unsaturated carbonyl compound according to any one of claims 1 to 9.

11. The rearrangement of the epoxide to the allylic alcohol is carried out by a reaction of the formula Zn(aa) ２ 11. The process of claim 10, wherein the process is carried out in the presence of an aminophenol and a catalyst represented by the formula:

12. 12. The method of claim 11, wherein the α-amino acid is selected from the group consisting of proline, valine, lysine, D-proline, D-valine, D-lysine L-proline, L-valine, L-lysine, 2-phenylglycine, phenylalanine, 2-amino-2-methylpropanoic acid, and mixtures thereof, and the aminophenol is selected from the group consisting of 2-aminophenol, 2-aminomethylphenol, and mixtures thereof.

13. The rearrangement of the epoxide to the allylic alcohol is carried out by a reaction of the formula Zn(carboxylate) ２ 11. The process according to claim 10, carried out in the presence of a catalyst represented by the formula:

14. 14. The method of any one of claims 10 to 13, wherein the epoxide is 1,2-limonene oxide.

15. 1. A catalyst system comprising: i) Formula [Zr(L)(X) ｒ ] (I) or [Zr(L') ｐ (X) ｎ ](I′) wherein L is a bisphenolate, triphenolate, or calixarene having at least four phenolic units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least four phenolic units; ii) a hydrogen acceptor; and

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