Process for preparation of allylic alcohols

Abstract

The present invention relates to the field of organic synthesis, and more particularly, to a process for rearranging an epoxide to an allylic alcohol in the presence of a zinc catalyst and aminophenol.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and more particularly, to a method for rearranging epoxides to allylic alcohols in the presence of a zinc catalyst and aminophenol. Background Art

[0002] Allylic alcohols represent highly desirable scaffolds that can be used directly or as key intermediates for the preparation of more complex compounds, applied in fields such as perfumery (cosmetic fragrance), cosmetics, pharmaceuticals, or agrochemistry. In particular, carveol is a valuable compound, known as a flavoring ingredient and can also serve as a key intermediate for the preparation of more complex compounds. Carveol can be obtained by the rearrangement of limonene oxide (a renewable carbon source), thus avoiding the use of petrochemical raw materials. In today's context of growing demand for green, low environmental and social impact products, this approach is particularly sought after. US2003065230 and WO2021151790 disclose the rearrangement of epoxides to allylic alcohols, where the rearrangement is carried out in the presence of a zinc catalyst and an activator. However, the reported conditions require a temperature of at least 200 °C to achieve complete conversion and good yields. Such high temperatures may be difficult to achieve industrially and require a large amount of energy. In addition, US2003065230 and WO2021151790 report a one-pot rearrangement of epoxides followed by oxidation to obtain enones. The oxidation is carried out in the presence of a hydrogen acceptor (also known as a sacrificial agent). The hydrogen acceptor is added in incremental amounts, and then the formed alcohol and unreacted hydrogen acceptor are removed after each increment. At the end of the process, the hydrogen acceptor or the corresponding alcohol is not recovered or reused.

[0003] Therefore, there is a need today to develop sustainable processes while reducing energy consumption and waste generation.

[0004] The present invention allows the rearrangement of epoxides to allylic alcohols under catalytic conditions and at lower temperatures without affecting the yield, while reducing the formation of by-products. In addition, the present invention allows the rearrangement of epoxides to allylic alcohols in the presence of a hydrogen acceptor under catalytic conditions, followed by oxidation under catalytic conditions, thereby obtaining the desired compound in high yield while limiting waste generation and even allowing the recovery and reuse of the hydrogen acceptor or the corresponding alcohol. To our knowledge, no currently reported technology can combine these two steps to produce the corresponding α-β unsaturated compounds in a one-pot process with high yield and sustainability. Summary of the Invention

[0005] The present invention relates to a new method never reported or implied in the prior art, which allows the preparation of allylic alcohols from raw materials containing renewable carbon under mild conditions.

[0006] Accordingly, a first object of the present invention is a method for rearranging an epoxide to an allylic alcohol, wherein the method is carried out in the presence of the following substances:

[0007] i) A catalyst of the formula Zn(aa)2, wherein aa is an α-aminocarboxylate having at least 3 carbon atoms, or a β-aminocarboxylate; and

[0008] ii) Aminophenol.

[0009] Another object of the present invention is a method for rearranging an epoxide to an allylic alcohol, wherein the method is carried out in the presence of the following substances:

[0010] i) A catalyst of the formula Zn(carboxylate)2; and

[0011] ii) Aminophenol;

[0012] wherein the molar ratio of the catalyst of the formula Zn(carboxylate)2 to aminophenol is from 1:3 to 1:5.

[0013] Another object of the present invention is a catalytic system comprising or consisting of the following substances:

[0014] i) A catalyst of the formula Zn(aa)2, wherein aa is an α-aminocarboxylate having at least 3 carbon atoms, or a β-aminocarboxylate; and

[0015] ii) Aminophenol. DETAILED DESCRIPTION

[0016] Surprisingly, it has now been found that, in the presence of a zinc catalyst and aminophenol, allylic alcohols can be prepared in an advantageous manner by rearrangement of epoxides. These unprecedented conditions allow the formation of α,β-unsaturated carbonyl compounds in extremely high yields without the need for high temperatures. In addition, the conditions of the present invention can be used in a one-step process, in which the epoxide is rearranged to an allylic alcohol and then oxidized in the presence of a zirconium catalyst and a hydrogen acceptor. This one-step process can be carried out at lower temperatures, allows the use of a wider range of hydrogen acceptors, while avoiding the formation of by-products and allowing the recovery of the excess hydrogen acceptor and the reduced product (i.e., the corresponding alcohol).

[0017] Accordingly, a first object of the present invention is a method for rearranging an epoxide to an allylic alcohol, wherein the method is carried out in the presence of the following substances:

[0018] iii) A catalyst of the formula Zn(aa)2, wherein aa is an α-aminocarboxylate having at least 3 carbon atoms, or a β-aminocarboxylate; and

[0019] iv) Aminophenol.

[0020] For the sake of clarity, the expression "α - aminocarboxylate having at least 3 carbon atoms" or a similar expression refers to the normal meaning understood by those skilled in the art, that is, a compound of the formula R a R b C(NHR c )COO - wherein at least one of R a , R b and R c contains at least one carbon atom. In other words, an α - aminocarboxylate is a carboxylate in which the carbon at the α - position of the carboxylate is substituted with an amine functional group, provided that the α - aminocarboxylate is not glycinate, i.e., CH2(NH2)COO - . An α - aminocarboxylate is an α - amino acid carboxylate. It should be understood that orotate is not covered by the term "α - aminocarboxylate".

[0021] For the sake of clarity, the expression "β - aminocarboxylate" or a similar expression refers to the normal meaning understood by those skilled in the art, that is, a carboxylate in which the carbon at the β - position of the carboxylate is substituted with an amine functional group.

[0022] According to any embodiment of the present invention, the epoxide is a compound of the following formula:

[0023]

[0024] The compound is in the form of any of its stereoisomers or a mixture thereof, and wherein R 1 is a hydrogen atom or a C 1-10 alkyl or a C 2-10 alkenyl, R 2 is a hydrogen atom or a C 1-3 alkyl, R 3 is a hydrogen atom or a C 1-5 alkyl; or R 1 and R 3 together represent a C 2-16 alkanediyl or a C 3-16 alkenediyl; or R 2 and R 3 together represent a C 2-16 alkanediyl; or R 1 and R 2 together represent a C 2-16 alkanediyl or a C 3-16 alkenediyl.

[0025] According to any embodiment of the present invention, the epoxide is a compound of the following formula:

[0026]

[0027] The compound is in the form of any of its stereoisomers or a mixture thereof, and wherein R 1 is C 1-10 alkyl, R 2 is a hydrogen atom or C 1-3 alkyl, R 3 is C 1-3 alkyl; or R 1 and R 3 together represent C 2-16 alkanediyl or a group; or R 2 and R 3 together represent C 2-16 alkanediyl; or R 1 and R 2 together represent C 2-16 alkanediyl.

[0028] According to any embodiment of the present invention, the allylic alcohol is a compound of the following formula:

[0029]

[0030] The compound is in the form of any of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 and R 3 have the same meanings as defined above.

[0031] For the sake of clarity, by the expression "any of its stereoisomers or a mixture thereof" or a similar expression, it means the normal meaning understood by those skilled in the art, that is, the compound cited in the present invention can be a pure enantiomer or a mixture of multiple enantiomers. In other words, the compound cited in the present invention can have at least one stereocenter, and this stereocenter can have two different stereochemistries (such as R or S). For example, the R 1 group can contain at least one stereocenter. The compound can even be in the form of a pure enantiomer or a mixture of multiple enantiomers. When the compound has more than one stereocenter, the compound cited in the present invention can even be in the form of a pure diastereomer or a mixture of multiple diastereomers. The compound can be in the racemic form or the non-racemic (scalemic) form. Therefore, the compound can be a stereoisomer or in the form of a substance composition containing various stereoisomers or consisting of various stereoisomers.

[0032] The wavy line indicates that the double bond can be in the form of its E or Z isomer, or a mixture thereof; for example, the present invention encompasses a substance composition comprising one or more compounds of formula (II) having the same chemical structure but different double bond configurations.

[0033] According to any of the above embodiments of the present invention, the compound of formula (II) can be in the form of its E or Z isomer, or a mixture thereof; for example, the present invention encompasses a substance composition comprising one or more compounds of formula (II) having the same chemical structure but different double bond configurations.

[0034] The terms "alkyl", "alkenyl" or "alkoxy" should be understood to include straight-chain or branched-chain alkyl, alkenyl or alkoxy. The terms "alkanediyl" or "alkenediyl" should be understood to include straight-chain, branched-chain, cycloaliphatic or cyclic alkanediyl or alkenediyl. The terms "alkenyl", "alkenediyl" and "cycloalkenyl" should be understood to include 1, 2 or 3 olefinic double bonds, preferably 1 or 2 olefinic double bonds, and even more preferably 1 double bond. The term "cycloalkenyl" should be understood to include monocyclic or fused, spiro and / or bridged bicyclic or tricyclic cycloalkenyl, preferably monocyclic cycloalkenyl.

[0035] According to any of the above embodiments, R 1 can be a hydrogen atom, C 1-8 alkyl or C 2-8 alkenyl. In particular, R 1 can be a hydrogen atom, C 1-6 alkyl or C 2-6 alkenyl. In particular, R 1 can be a hydrogen atom, C 1-4 alkyl or C 4-6 alkenyl. In particular, R 1 can be a hydrogen atom, C 1-3 alkyl or C 4-6 alkenyl. In particular, R 1 can be a hydrogen atom, C 1-3 alkyl or C 4-6 alkenyl. In particular, R 1 can be a hydrogen atom, C 1-3 alkyl or C 4-6 alkenyl. In particular, R 1 can be a hydrogen atom, C 1-2 alkyl or C6 alkenyl. Even more particularly, R 1 can be a hydrogen atom or methyl, ethyl, hex-3-en-1-yl or 4-methylpent-3-en-1-yl.

[0036] According to any of the above embodiments, R 3 can be a hydrogen atom or C 1-5 alkyl. In particular, R 3 can be a hydrogen atom, C1-3 an alkyl or pentyl group. In particular, R 3 can be a hydrogen atom or a methyl, ethyl or pentyl group. In particular, R 3 can be a hydrogen atom or a pentyl group. Even more particularly, R 3 can be a hydrogen atom or a straight-chain pentyl group.

[0037] According to any of the above embodiments, R 2 can be a hydrogen atom or a C 1-2 alkyl group. In particular, R 2 can be a hydrogen atom or a methyl group. Even more particularly, R 2 can be a methyl group.

[0038] According to any of the above embodiments, R 1 together with R 2 represents a C 2-12 alkanediyl or a C 3-12 alkenediyl group. In particular, R 1 together with R 2 represents a C 2-10 alkanediyl or a C 3-10 alkenediyl group. In particular, R 1 together with R 2 represents a C 2-8 alkanediyl or a C 3-8 alkenediyl group. In particular, R 1 together with R 2 represents a C 4-8 alkanediyl or a C 4-8 alkenediyl group. In particular, R 1 together with R 2 forms a C 5-6 cycloalkenyl group, which may optionally be substituted with a C 1-4 alkyl or alkenyl group. Even more particularly, R 1 together with R 2 represents 2-isopropenyl-1,4-butadienyl or a group of formula (a):

[0039]

[0040] The compound is in the form of any of its stereoisomers or a mixture thereof.

[0041] According to any of the above embodiments, R 2 together with R 3 represents a C 2-12 alkanediyl group. In particular, R 2 together with R 3 represents a C 2-10 alkanediyl group. In particular, R 2 together with R 3Together represent C 2-8 alkanediyl. In particular, R 2 and R 3 together represent C 4-8 alkanediyl. In particular, R 2 and R 3 together represent C 6-8 alkanediyl. Even more particularly, R 2 and R 3 together represent a group of formula (a):

[0042]

[0043] The compound is in the form of any one of its stereoisomers or a mixture thereof.

[0044] According to any one of the above embodiments, R 1 and R 3 together represent C 2-12 alkanediyl or C 3-12 alkenediyl. In particular, R 1 and R 3 together represent C 2-10 alkanediyl or C 3-10 alkenediyl. In particular, R 1 and R 3 together represent C 2-8 alkanediyl or C 3-8 alkenediyl. In particular, R 1 and R 3 together represent C 4-8 alkanediyl or C 4-8 alkenediyl. In particular, R 1 and R 3 together represent C 5-8 alkanediyl or C 5-8 alkenediyl. In particular, R 1 and R 3 together represent C 5-7 alkanediyl or C 5-7 alkenediyl. In particular, R 1 and R 3 together represent C6 alkanediyl or C6 alkenediyl. Even more particularly, R 1 and R 3 together represent 2-isopropenyl-1,3-propanediyl, a group of formula (b) or a group of formula (c):

[0045]

[0046] The compound is in the form of any one of its stereoisomers or a mixture thereof.

[0047] According to any of the above embodiments, R 1 and R 3 together represent C 2-12 alkanediyl or C 3-14 alkenediyl, and R 2 is a hydrogen atom or C 1-3 alkyl. In particular, R 1 and R 3 together represent C 2-8 alkanediyl or C 4-12 alkenediyl, and R 2 is a hydrogen atom or C 1-3 alkyl. In particular, R 1 and R 3 together represent C 2-6 alkanediyl or C 4-10 alkenediyl, and R 2 is a hydrogen atom or C 1-3 alkyl. In particular, R 1 and R 3 together represent C 2-4 alkanediyl or C 4-8 alkenediyl, and R 2 is a hydrogen atom or C 1-3 alkyl. In particular, R 1 and R 3 together represent C 2-4 alkanediyl or C 4-8 alkenediyl, and R 2 is a hydrogen atom or C 1-2 alkyl. In particular, R 1 and R 3 together represent C 2-3 alkanediyl or C 5-7 alkenediyl, and R 2 is a hydrogen atom or C 1-2 alkyl. Even more particularly, R 1 and R 3 together represent C3 alkanediyl or C6 alkenediyl, and R 2 is methyl.

[0048] According to any of the above embodiments of the present invention, non-limiting examples of the epoxide are 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 2,4Octane, 2-isopropyl-5-methyl-7-oxabicyclo[4.1.0]heptane, 4-isopropyl-1-methyl-7-oxabicyclo[4.1.0]heptane, alpha-pinene oxide, beta-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.

[0049] According to any of the above embodiments of the present invention, non-limiting examples of the allylic alcohol are carveol, 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol, 3,7,7-trimethylbicyclo[4.1.0]hept-3-en-2-ol, 6-isopropyl-3-methylcyclohex-2-en-1-ol, 5-isopropyl-2-methylcyclohex-2-en-1-ol, 6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-3-ol, (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol.

[0050] According to any embodiment of the present invention, the alpha-aminocarboxylate has at least 4 carbon atoms, preferably at least 5 carbon atoms, and even more preferably at least 6 carbon atoms.

[0051] According to any embodiment of the present invention, the alpha-aminocarboxylate is of the formula R a R b C(NHR c )COO - wherein R a is a C 1-18 hydrocarbon optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups, R b is a hydrogen atom or a C 1-18 hydrocarbon optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups, and R c is a hydrogen atom or a C 1-18 hydrocarbyl group; or R a and R c together represent a C 3-11 alkanediyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, or alcohol groups. When R c is a C 1-18 hydrocarbon containing one or two carbonyl functional groups, the carbonyl functional group is not directly connected to NH.

[0052] It should be understood that by “…hydrocarbyl…”, it is meant that the group consists of hydrogen and carbon atoms and can be in the form of an aliphatic hydrocarbon, i.e., a straight-chain or branched-chain saturated hydrocarbon (e.g., an alkyl group), a straight-chain or branched-chain unsaturated hydrocarbon (e.g., an alkenyl or alkynyl group), a saturated cycloalkane (e.g., a cycloalkyl group) or an unsaturated cycloalkane (e.g., a cycloalkenyl or cycloalkynyl group), or can be in the form of an aromatic hydrocarbon, i.e., an aryl group, or can also be in the form of a mixture of the aforementioned types of groups. For example, unless specifically restricted to only one of the mentioned types, a particular group can contain a straight-chain alkyl group, a branched-chain alkenyl group (e.g., having one or more carbon-carbon double bonds), a (poly)cycloalkyl group and an aryl moiety. Similarly, in all embodiments of the present invention, when a group is mentioned as being in more than one type of topology (e.g., straight-chain, cyclic or branched) and / or saturation or unsaturation (e.g., alkyl, aromatic or alkenyl) form, it also means a group that can contain moieties having any one of the aforementioned topologies or saturation or unsaturation as explained above. Similarly, in all embodiments of the present invention, when a group is mentioned in one form of saturation or unsaturation (e.g., an alkyl group), it means that the group can be of any type of topology (e.g., straight-chain, cyclic or branched) or have several moieties with various topologies.

[0053] It should be understood that the term “…hydrocarbyl, optionally containing…” means that the hydrocarbyl optionally contains an alcohol, a ketone, an aldehyde, an ether, an ester, a carboxylic acid, an amine, an amide, a carbamate or a nitrile. These groups can replace a hydrogen atom of the hydrocarbyl and thus be attached to the hydrocarbon sidewise, or replace a carbon atom of the hydrocarbyl (if chemically possible) and thus be inserted into the hydrocarbon chain. For example, the -CH2-CH2-CHOH-CH2- group represents a C4 hydrocarbyl group containing an alcohol group (hydrogen atom replaced); similarly, the -CH2-CH2-O-CH2-CH2-O-CH2-CH2- group represents a C6 hydrocarbyl group containing two ether groups (carbon atoms replaced / inserted into the hydrocarbon chain).

[0054] The term “optionally” should be understood to mean that a group can or cannot contain a certain functional group or substituent.

[0055] In any embodiment of the present invention, R a can be a C 1-15 hydrocarbon optionally containing one or two functional groups selected from the group consisting of an ether, an ester, a carbonyl, an amine, an amide, an alcohol, a hydroxyl, a thioether, and a carboxylic acid group. In particular, R a can be a C 1-12 hydrocarbyl group optionally containing one or two functional groups selected from the group consisting of an ether, an ester, a carbonyl, an amine, an amide, an alcohol, a hydroxyl, a thioether, and a carboxylic acid group. In particular, R a can be a C1-10 Hydrocarbyl. In particular, R a may be a C hydrocarbyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-8 Hydrocarbyl. In particular, R a may be phenyl, benzyl or a C alkyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-8 alkyl. More particularly, R a may be phenyl, benzyl or a C alkyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-6 alkyl.

[0056] According to any embodiment of the present invention, R b may be a hydrogen atom or a C hydrocarbyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-15 Hydrocarbyl. In particular, R b may be a hydrogen atom or a C hydrocarbyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-12 Hydrocarbyl. In particular, R b may be a hydrogen atom or a C hydrocarbyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-10 Hydrocarbyl. In particular, R b may be a hydrogen atom or a C hydrocarbyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-8 Hydrocarbyl. In particular, R b may be a hydrogen atom or a C hydrocarbyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups 1-8 alkyl. In particular, R b may be a hydrogen atom or a C 1-6 alkyl. In particular, R b may be a hydrogen atom or a C 1-4 alkyl. In particular, R b may be a hydrogen atom or a C 1-3 alkyl. In particular, R b may be a hydrogen atom or a C 1-2 alkyl. In particular, R b may be a hydrogen atom or methyl. Even more particularly, R b may be a hydrogen atom.

[0057] According to any embodiment of the present invention, Rc may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R 1-15 may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R c may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R 1-12 may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R c may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R 1-10 may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R c may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R 1-8 may be a hydrogen atom or a C hydrocarbon group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R c may be a hydrogen atom, a phenyl group, a benzyl group or a C alkyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R 1-8 may be a hydrogen atom, a phenyl group, a benzyl group or a C alkyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R c may be a hydrogen atom or a C alkyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R 1-8 may be a hydrogen atom or a C alkyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups. In particular, R c may be a hydrogen atom or a C alkyl group. In particular, R 1-6 may be a hydrogen atom or a C alkyl group. In particular, R c may be a hydrogen atom or a C alkyl group. In particular, R 1-4 may be a hydrogen atom or a C alkyl group. In particular, R c may be a hydrogen atom or a C alkyl group. In particular, R 1-3 may be a hydrogen atom or a C alkyl group. In particular, R c may be a hydrogen atom or a C alkyl group. In particular, R 1-2 may be a hydrogen atom or a C alkyl group. In particular, R c may be a hydrogen atom or a methyl group. Even more particularly, R c may be a hydrogen atom.

[0058] According to any embodiment of the present invention, R a and R c when combined together may be a C alkanediyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide or alcohol groups. In particular, R 3-10 and R a when combined together may be a C alkanediyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide or alcohol groups. In particular, R c and R 3-8 when combined together may be a C alkanediyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide or alcohol groups. In particular, R a and R c when combined together may be a C alkanediyl group3-6 alkanediyl. In particular, R a together with R c may be C 4-6 alkanediyl. Even more particularly, R a together with R c may be C 5-6 alkanediyl.

[0059] According to any embodiment of the present invention, the α-aminocarboxylate has 4 to 10 carbon atoms.

[0060] According to any embodiment of the present invention, the α-aminocarboxylates may be different or the same.

[0061] According to any embodiment of the present invention, the α-aminocarboxylate may be derived from α-amino acids of natural or artificial origin and may be selected from the group of natural α-amino acids such as S-alanine or R-alanine (R a = CH3; R b and R c = H), S-asparagine or R-asparagine (R a = CH2CONH2; R b and R c = H), S-glutamine or R-glutamine [R a = (CH2)2CONH2; R b and R c = H], S-isoleucine or R-isoleucine [R a = C(CH3)CH2CH3; R b and R c = H], S-leucine or R-leucine [R a = CH2CH(CH3)2; R b and R c = H], S-lysine or R-lysine [R a = (CH2)4NH2; R b and R c = H], S-methionine or R-methionine [R a = (CH2)2SCH3; R b and R c = H], S-phenylalanine or R-phenylalanine (R a = CH2C6H5; R b and R c = H), S-serine or R-serine (R a = CH2OH; R b and R c = H), S-tyrosine or R-tyrosine (R a=CH2C6H4OH; R b and R c =H), S-proline or R-proline (R a together with R c =CH2CH2CH2; R b =H); S-valine or R-valine [R a =CH(CH3)2; R b and R c =H), S-aspartic acid or R-aspartic acid (R a =CH2COOH; R b and R c =H), and S-glutamic acid or R-glutamic acid [R a =(CH2)2COOH; R b and R c =H], or an artificial α-amino acid selected from the group consisting of: norleucine [R a =(CH2)3CH3; R b and R c =H], norvaline [R a =(CH2)2CH3; R b and R c =H], 2-phenylglycine (R a =C6H5; R b and R c =H), ornithine [R a =(CH2)3NH; R b and R c =H2], homoalanine [R a =CH2CH3; R b and R c =H], 2-amino-2-methylpropanoic acid (R a and R b =CH3; R c =H] and homoserine [R a =(CH2)2OH; R b and R c =H]. In particular, the α-aminocarboxylate may be derived from an α-amino acid selected from the group consisting of proline, valine, lysine, 2-phenylglycine, phenylalanine, 2-amino-2-methylpropanoic acid, and mixtures thereof.

[0062] According to any embodiment of the present invention, the β-aminocarboxylate is anthranilate.

[0063] 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-tert-butylphenol, and mixtures thereof.

[0064] Alternatively, the method for rearranging an epoxide to an allylic alcohol according to the present invention can be carried out in the presence of a catalyst of the formula Zn(carboxylate)2. Therefore, another object of the present invention is to provide a method for rearranging an epoxide to an allylic alcohol, wherein the method is carried out in the presence of:

[0065] i) a catalyst of the formula Zn(carboxylate)2; and

[0066] ii) an aminophenol;

[0067] wherein the molar ratio of the catalyst of the formula Zn(carboxylate)2 to the aminophenol is from 1:3 to 1:5.

[0068] The term "carboxylate" should be understood to include ligands containing the COO functional group. In particular, the carboxylate conforms to the formula R d COO, where R d is C 1-18 alkyl or C 6-10 aryl, especially C 1-16 alkyl. The carboxylate can be selected from the group consisting of acetate, octanoate, 2-ethylhexanoate, laurate, palmitate, stearate, 2-octyldodecanoate, benzoate, naphtenate.

[0069] The term "aryl" has its conventional meaning in the art, i.e., an optionally substituted aromatic hydrocarbon group, such as phenyl or naphthyl. Non-limiting examples of optional substituents of the aryl include C 1-3 alkyl or alkoxy, hydroxyl or halogen atoms.

[0070] According to any embodiment of the present invention, the ratio of the catalyst of the formula Zn(carboxylate)2 to the aminophenol is from 1:3 to 1:4.

[0071] According to any embodiment of the present invention, the epoxide, allylic alcohol, and aminophenol have the same meanings as defined above.

[0072] Catalysts of the formula Zn(aa)2 or Zn(carboxylate)2 can be added to the reaction medium of the method of the present invention to form allylic alcohols over a wide range of concentrations. As non-limiting examples, catalyst concentration values in the range of 0.1 mol% to 10 mol% relative to the total amount of the epoxide can be cited. In particular, the catalyst concentration can be 0.25 mol% to 5 mol%. Needless to say, the method is also applicable to more catalysts. However, as is known to those skilled in the art, the optimal concentration of the catalyst will depend on the nature of the catalyst, the nature of the epoxide, the reaction temperature, and the required reaction time.

[0073] Catalysts of the formula Zn(aa)2 are commercially available compounds or can be prepared by a variety of methods, such as the method reported in Polymers (Basel, Switzerland) (2019), 11(5), 790. Alternatively, catalysts of the formula Zn(aa)2 are formed in situ by the reaction of ZnO with 2 equivalents of AA.

[0074] Catalysts of the formula Zn(carboxylate)2 are commercially available compounds or can be prepared by a variety of methods, such as the method reported in Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (2008), 70A(1), 217. Alternatively, catalysts of the formula Zn(carboxylate)2 are formed in situ by the reaction of ZnO with 2 equivalents of carboxylic acid.

[0075] Aminophenol can be added to the reaction medium of the method of the present invention to form allylic alcohols over a wide range of concentrations. As non-limiting examples, aminophenol concentration ranges of 1 mol% to 5 mol%, and even 1 mol% to 3 mol% relative to the amount of the epoxide can be cited. Needless to say, the method is also applicable to more aminophenol. However, as is known to those skilled in the art, the optimal concentration of aminophenol will depend on the nature of aminophenol, the nature of the epoxide, the nature of the catalyst, the reaction temperature, and the required reaction time.

[0076] According to any embodiment of the present invention, the method of the present invention for rearranging an epoxide to an allylic alcohol is carried out at a temperature of 160 °C to 190 °C. In particular, the temperature is in the range of 170 °C to 190 °C. Of course, those skilled in the art can also select a preferred temperature based on the melting and boiling points of the starting and final products and the required reaction or conversion time.

[0077] The method of the present invention for rearranging an epoxide to an allylic alcohol can be carried out with or without a solvent. When a solvent is needed or used for practical reasons, any solvent existing in such reactions can be used for the purposes of the present invention. Non-limiting examples include C 6-12Aromatic solvents such as xylene, toluene, 1,3 - diisopropylbenzene, cumene or pseudocumene, or mixtures thereof, hydrocarbon solvents such as limonene, decane, dodecane or heavier hydrocarbon solvents, or mixtures thereof. The choice of solvent depends on the nature of the substrate and / or the catalyst, and those skilled in the art can select the most suitable solvent according to the specific situation to optimize the reaction.

[0078] The method for rearranging an epoxide to an allylic alcohol according to the present invention can be carried out under batch or continuous conditions.

[0079] The method for rearranging an epoxide to an allylic alcohol according to the present invention can be carried out at atmospheric pressure.

[0080] According to any embodiment of the present invention, the method of the present invention further comprises the step of oxidizing the allylic alcohol obtained by the above method into an α,β - unsaturated carbonyl compound.

[0081] According to any embodiment of the present invention, the α,β - unsaturated carbonyl compound is a compound of the following formula:

[0082]

[0083] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 、R 2 and R 3 have the same meanings as defined above.

[0084] According to any embodiment of the present invention, the α,β - unsaturated carbonyl compound is carvone.

[0085] According to any embodiment of the present invention, the oxidation is carried out in the presence of a zirconium catalyst and a hydrogen acceptor.

[0086] According to any embodiment of the present invention, the zirconium catalyst conforms to the following formula:

[0087] [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’)

[0088] wherein L is bisphenolate, triphenolate or a calixarene having at least 4 phenol units, L’ is 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, and r is 2 when L is bisphenolate, or r is 1 when L is triphenolate, or r is 0 when L is a calixarene having at least 4 phenol units.

[0089] According to any embodiment of the present invention, the phenoxide is selected from the group consisting of 2-nitrophenoxide, o-cresoxide, 2-(trifluoromethyl)phenoxide, and 2-cyanophenoxide.

[0090] According to any embodiment of the present invention, the bisphenoxide can be selected from the group consisting of, but not limited to: [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).

[0091] According to any embodiment of the present invention, the anionic ligands can each independently be a halogen atom, a β-diketonate, an OOCR 7 group or an OR 8 group, where R 7 is a C 1-10 alkyl, benzyl, naphthyl, or a phenyl optionally substituted with a hydroxyl group, and R 8 is a C 1-6 alkyl. The term "β-diketonate" should be understood to include ligands containing a C(=O)-CH=C(O - ) group. In particular, the β-diketonate conforms to the formula R 9 -C(=O)-CH=C(O - )-R 10 , where R 9 and R 10 are each independently a C 1-6 alkyl, particularly a C 1-4 alkyl, even more particularly methyl, propyl, isopropyl, or tert-butyl. Non-limiting examples of β-diketonates can include 4-oxopent-2-ene-2-carboxylate, 2,2-dimethyl-5-oxohex-3-ene-3-carboxylate, 2,6-dimethyl-5-oxohept-3-ene-3-carboxylate, or 2,2,6,6-tetramethyl-5-oxohept-3-ene-3-carboxylate. In particular, R 7 can be a C 1-8 alkyl, particularly a C 1-6 alkyl, even more particularly a C 1-5 alkyl. In particular, R 8 can be a C 1-4 alkyl, particularly propyl, isopropyl, butyl, or tert-butyl. In particular, the anionic ligand is selected from the group consisting of acetylacetonate.

[0092] According to a specific embodiment, when p is 0 and n is 4, X is an alkoxide of the formula OR as defined above. 9

[0093] According to any embodiment of the present invention, the catalyst of formula (IV) can be selected from the group consisting of: bis(2,4-pentanedionato)zirconium [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolato]]; bis(2,4-pentanedionato)zirconium [2,2'-methylenebis[(4-6-di-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-methylenebis[(4-6-dimethyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-ethylenebis[(4-6-di-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-thiobis[(4-methyl-6-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-oxybis[(4-methyl-6-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [[2,2'-binaphthalene]-1,1'-diolate]; bis(propanolate)zirconium [[2,2'-binaphthalene]-1,1'-diolate]; bis(propanolate)zirconium [[2,2'-biphenyl]-1,1'-diolate].

[0094] The catalyst represented by formula (IV) or formula (IV') can be added to the reaction medium of the method of the present invention to form α,β-unsaturated carbonyl compounds in a wide concentration range. As a non-limiting example, a catalyst concentration in the range of 0.1 mol% to 10 mol% relative to the total amount of allylic alcohol can be cited. In particular, the catalyst concentration can be 0.5 mol% to 5 mol%. Needless to say, the method is also applicable to more catalysts. However, it is known to those skilled in the art that the optimal concentration of the catalyst will depend on the nature of the catalyst, the nature of the allylic alcohol, the reaction temperature, and the required reaction time.

[0095] According to any embodiment of the present invention, the hydrogen acceptor is 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.

[0096] A hydrogen acceptor can be added to the reaction medium of the method of the present invention to form α,β-unsaturated carbonyl compounds in a wide range of concentrations. As non-limiting examples, concentration values of the hydrogen acceptor in the range of 1 equivalent to 5 equivalents, and even 1 equivalent to 2 equivalents, relative to the amount of allylic alcohol can be cited. Needless to say, the method is also applicable to a greater amount of hydrogen acceptor. However, as is known to those skilled in the art, the optimal concentration of the hydrogen acceptor will depend on the nature of the hydrogen acceptor, the nature of the allylic alcohol, the reaction temperature, and the required reaction time.

[0097] According to any embodiment of the present invention, the method for oxidizing an allylic alcohol to an α,β-unsaturated carbonyl compound of the present invention is carried out at a temperature of 50 °C to 190 °C. In particular, the temperature is in the range of 100 °C to 140 °C. Of course, those skilled in the art are also able to select a preferred temperature based on the melting and boiling points of the starting and final products and the required reaction or conversion time.

[0098] The method for oxidizing an allylic alcohol to an α,β-unsaturated carbonyl compound of the present invention can be carried out with or without a solvent. When a solvent is needed or used for practical reasons, any solvent existing in such reactions can be used in the present invention. Non-limiting examples include C 6-12 aromatic solvents such as xylene, toluene, 1,3-diisopropylbenzene, cumene or pseudocumene, or mixtures thereof, hydrocarbon solvents such as cyclohexane, heptane, or mixtures thereof. The choice of solvent depends on the nature of the substrate and / or the catalyst, and those skilled in the art are able to select the most suitable solvent according to the specific circumstances to optimize the reaction.

[0099] The method for oxidizing an allylic alcohol to an α,β-unsaturated carbonyl compound of the present invention can be carried out under batch or continuous conditions.

[0100] The method for oxidizing an allylic alcohol to an α,β-unsaturated carbonyl compound of the present invention can be carried out at atmospheric pressure.

[0101] According to a specific embodiment of the present invention, the rearrangement of an 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" should be understood to mean that the two steps are carried out continuously 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 can also be generated in situ after the first step is completed.

[0102] Another object of the present invention is a catalytic system comprising or consisting of the following substances:

[0103] i) a catalyst of the formula Zn(aa)2, where aa is an α-amino carboxylate having at least 3 carbon atoms, or a β-amino carboxylate; and

[0104] ii) aminophenol.

[0105] According to any embodiment of the present invention, the catalytic system as defined above is suitable for the method of rearranging an epoxide to an allylic alcohol as defined above.

[0106] Another object of the present invention is the use of a catalytic system in the method of rearranging an epoxide to an allylic alcohol, the catalytic system comprising or consisting of the following substances:

[0107] i) a catalyst of formula Zn(aa)2, where aa is an α-aminocarboxylate having at least 3 carbon atoms, or a β-aminocarboxylate; and

[0108] ii) aminophenol.

[0109] A typical way of carrying out the method of the present invention is reported below in the examples.

[0110] Examples

[0111] The present invention will now be described in more detail by the following examples, where the abbreviations have their conventional meanings in the art and the temperature is expressed in degrees Celsius (°C). The preparation of the precatalyst and ligand solutions was carried out using standard Schlenk techniques under an inert atmosphere (argon). The solvents were dried by conventional methods and distilled under an argon atmosphere. The NMR of all prepared compounds was consistent with the NMR reported in the literature.

[0112] Example 1

[0113] Rearrangement of 1,2-epoxy-limonene to carveol under the conditions of the present invention and comparative conditions

[0114] A mixture of limonene oxide (60% cis isomer and 40% trans isomer), a zinc catalyst, and 2-aminophenol (2-AP) (the equivalent ratio of AP / Zn is detailed in Table I) was heated to 185 °C in a glass reactor equipped with a stirrer, a thermometer, a Dean-Stark water separator, and a condenser. During the entire reaction process, the internal temperature was maintained at 185 °C. Then, the crude product was flash distilled to determine the amount of residue formed during the reaction, and the yield was calculated based on the gas chromatographic purity of the distilled product. The conversion rate, selectivity (the sum of carveol and carvone / conversion rate), and isolated yield are listed in Table 1.

[0115] Table 1: Rearrangement of limonene oxide to carveol using the conditions of the present invention and comparative conditions

[0116]

[0117] a) The ratio of 2-AP / Zn as described in WO03 / 004448 and WO 2021151790.

[0118] b) The reaction is carried out at 200 °C instead of 185 °C.

[0119] Example 2

[0120] Preparation of R-(−)-carvone by one-pot sequential rearrangement of R-(+)-1,2-epoxy-limonene using Zn(L-prolinate)2 as a catalyst and Oppenauer oxidation of R-(−)-carveol in the presence of [2,2'-Methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium and cyclohexanone as a hydrogen acceptor

[0121] A mixture of R-(+)-1,2-epoxy-limonene (R-LMO), Zn(L-prolinato)2 (0.25 mol.%), and 2-aminophenol (4 equivalents / Zn) is heated at 185 °C for 9 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark water separator, and condenser. After completion of the rearrangement step, the reaction mixture is cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and cyclohexanone in an amount of 1.1 equivalents relative to the initial R-LMO are added. The reaction mixture is heated at 130 °C for 4 h to complete the conversion of carveol to carvone. Carvone is obtained by distillation in a yield of 99% based on the weighed amount of the intermediate carveol and 82% based on the initial R-LMO. The substance is purified by conventional methods to give R-(-)-carvone with a purity > 99 GC%.

[0122] Example 3

[0123] Preparation of R-(−)-carvone by one-pot sequential rearrangement of R-(+)-1,2-epoxy-limonene using Zn(L-prolinate)2 as a catalyst and Oppenauer oxidation of R-(−)-carveol in the presence of [2,2'-Methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium and benzaldehyde as a hydrogen acceptor Example 4

[0124] A mixture of R-(+)-1,2-epoxy-limonene (R-LMO), Zn(L-prolinato)2 (0.25 mol.%), and 2-aminophenol (4 equivalents / Zn) is heated at 185 °C for 9 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark water separator, and condenser. After completion of the rearrangement step, the reaction mixture is cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and benzaldehyde in an amount of 1.1 equivalents relative to the initial R-LMO are added. The reaction mixture is heated at 130 °C for 4 h to complete the conversion of carveol to carvone. Carvone is obtained by distillation in a yield of 96% based on the weighed amount of the intermediate carveol and 79% based on the initial R-LMO. The substance is purified by conventional methods to give R-(-)-carvone with a purity > 99 GC%.

[0125] Preparation of R-(−)-carvone by one-pot sequential rearrangement of R-(+)-1,2-epoxy-limonene using Zn(L-prolinate)2 as a catalyst and Oppenauer oxidation of R-(−)-carveol in the presence of

[0126] [2,2'-Methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium and benzaldehyde as a hydrogen acceptor Example 5 Preparation of R-(−)-carvone by one-pot sequential rearrangement of R-(+)-1,2-epoxy-limonene using Zn(2-ethylhexanoate)2 as a catalyst and Oppenauer oxidation of R-(−)-carveol in the presence of

[0127] A mixture of R-(+)-1,2-epoxy limonene (R-LMO), Zn(L-prolinate)2 (0.25 mol.%), and 2-aminophenol (4 equivalents / Zn) was heated at 185 °C for 9 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark water separator, and condenser. After the rearrangement step was completed, the reaction mixture was cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and benzaldehyde in an amount of 1.1 equivalents 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 another 2 h to complete the conversion of carveol to carvone. Carvone was obtained by distillation with a yield of 99% based on the weighed amount of the intermediate carveol and 82% based on the initial R-LMO. The substance was purified by a conventional method to obtain R-(-)-carvone with a purity > 99 GC%.

[0128] [2,2'-Methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium and benzaldehyde as a hydrogen acceptor

[0129] Example 6 Preparation of R-(−)-carvone by one-pot sequential rearrangement of R-(+)-1,2-epoxy-limonene using Zn(2-ethylhexanoate)2 as a catalyst and Oppenauer oxidation of R-(−)-carveol in the presence of in-situ generated [2,2'-Methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium and

[0130] A mixture of R-(+)-1,2-epoxy limonene (R-LMO), Zn(2-ethylhexanoate)2 (0.5 mol.%), and 2-aminophenol (3 equivalents / Zn) was heated at 185 °C for 15 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark water separator, and condenser. After the rearrangement step was completed, the reaction mixture was cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and benzaldehyde in an amount of 1.1 equivalents 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 another 2 h to complete the conversion of carveol to carvone. Carvone was obtained by distillation with a yield of 99% based on the weighed amount of the intermediate carveol and 83% based on the initial R-LMO. The substance was purified by a conventional method to obtain R-(-)-carvone with a purity > 99 GC%.

[0131] benzaldehyde as a hydrogen acceptor

[0132] Example 7 Trimethylbicyclo[4.1.0]hept-4-en-3-ol Example 8

[0133] In a glass reactor equipped with a stirrer, a thermometer, a Dean-Stark water separator and a condenser, a mixture of R-(+)-1,2-epoxy-limonene (R-LMO), Zn(2-ethylhexanoate)2 (0.5 mol.%), and 2-aminophenol (3 equivalents / Zn) was heated at 185 °C for 15 h. After the rearrangement step was completed, the reaction mixture was cooled to 30 °C. 1 mol.% of zirconium propoxide (Zr(propoxide)4) (70% propanol solution), 6,6'-methylenebis(2-(tert-butyl)-4-methylphenol), and 2.2 equivalents of acetylacetone were added, and the reaction mixture was stirred for 1 h. Then, benzaldehyde in an amount of 1.1 equivalents relative to the initial R-LMO was added. The reaction mixture was heated at 100 °C for 2 h and then at 130 °C for another 2 h to complete the conversion of carveol to carvone. Carvone was obtained by distillation in a yield of 99% based on the weighed amount of the intermediate carveol and 83% based on the initial R-LMO. After rectification, the excess benzaldehyde and the co-produced benzyl alcohol were recovered separately, and the total yield was 95% with a purity > 99%, while the yield of R-(-)-carvone was 98% with a purity > 99 GC%.

[0134] Rearrangement of α-epoxypinene to 6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-3-ol using the conditions of the present invention

[0135] The conditions for using the present invention rearrange 3,8,8-trimethyl-4-oxatricyclo[5.1.0.0 3,5 octane to 4,7,7- Example 9

[0136] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer, and a condenser, a mixture of 3,8,8-trimethyl-4-oxatricyclo[5.1.0.0 3,5 octane (5 g, 32 mmol), Zn(L-prolinate)2 (0.25 mol.%), and 2-aminophenol (4 equivalents / Zn) was heated at 185 °C for 5 h to complete the conversion. After distilling the residue, the product was obtained in a yield of 85% as a 70:30 mixture of 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol and 5-isopropenyl-2-methyl-cyclohex-3-en-1-ol.

[0137] Rearrangement of β-epoxypinene oxide to (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol using the conditions of the present invention

[0138] Example 10 Preparation of R-(−)-carvone by one-pot sequential rearrangement of R-(+)-1,2-epoxy-limonene and Oppenauer oxidation of R-(−)-carveol under the conditions of the present invention and comparative conditions

[0139] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer, and a condenser, a mixture of α-pinene oxide (5 g, 32 mmol), Zn(L-prolinate)2 (1 mol.%), and 2-aminophenol (3 equivalents / Zn) was heated at 190 °C for 7 h until the conversion reached 80 GC%. 2-Methylenebicyclo[3.1.1]hept-3-ol was obtained with a GC selectivity of 75%.

[0140] ​

[0141] ​ ​

[0142] A mixture of Zn(phenylglycinate)2 (60 mg, 0.16 mmol) and 2-aminophenol (4 equivalents / Zn) in 1,3-diisopropylbenzene (2 mL) was heated at 180 °C for 1 h in a Schlenk reactor equipped with a magnetic stirrer, a thermometer, and a condenser. Then β-ocimene (5 g, 32 mmol) was added slowly and heated for 6 h to achieve a conversion of 72 GC%. (6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol was obtained with a GC selectivity of 63%.

[0143] ​

[0144] ​ ​

[0145] A mixture of limonene 1,2-oxide (LMO, 60% cis isomer and 40% trans isomer, 400 g), a catalyst, and 2-aminophenol (2-AP) (the equivalents of 2-AP relative to Zn are shown in Table 2) was heated to the temperature specified in Table 2 in a glass reactor equipped with a stirrer, a thermometer, a Dean-Stark water separator, and a condenser. The temperature was maintained until the conversion of R-LMO > 96%. After cooling, an oxidation catalyst was added together with a hydrogen acceptor (the amounts used are shown in Table 2). In some embodiments, the hydrogen acceptor was added in batches after selectively removing the excess hydrogen acceptor (HA) and its corresponding alcohol. It should be clarified that if 2 / 2 is reported in the time column, it means that half of the total amount of HA was added first, and then after heating for 2 h at the reported temperature, the unreacted HA and its corresponding alcohol were removed by distillation, and then the operation was repeated; for example, 2 / 2 / 2 means that HA was added every 2 h for a total of 3 times. Then the crude carvone was purified by distillation to obtain carvone with a purity > 98%. The yields are reported in the column of isolated yields of carvone. The excess HA and its corresponding alcohol can also be distilled separately or together. If possible, their total yields ((moles of excess HA + moles of alcohol) / moles of initial total HA) are also reported.

[0146] Table 2: Rearrangement of limonene 1,2-oxide to carveol in one pot using the conditions of the present invention and comparative conditions, followed by oxidation and Oppenauer oxidation to obtain R-(-)-carvone

[0147]

[0148] 1) Conditions reported in WO2003004448

[0149] 2) Conditions reported in WO2021151790

[0150] 3) Conditions reported in WO2003004448, except for the oxidation temperature

[0151] 4) Conditions of the present invention

[0152] 5) 2,2'-Methylenebis[(4-methyl-6-tert-butyl)phenol]

[0153] 6) 1,2-Limonene oxide

[0154] Contrary to the prior art conditions, the conditions of the present invention can separate carvone in high yield while efficiently recovering the hydrogen acceptor or the corresponding alcohol. When the hydrogen acceptor is benzaldehyde, the resulting reduction product is benzyl alcohol, a valuable ingredient that can be used as a flavoring ingredient.

Claims

1. A method for rearranging an epoxide to an allylic alcohol, wherein the method is carried out in the presence of: i) a catalyst of the formula Zn(aa)2, wherein aa is an α - aminocarboxylate having at least 3 carbon atoms or a β - aminocarboxylate; and ii) an aminophenol.

2. The method according to claim 1, wherein the α-aminocarboxylate conforms to the formula R a R b C(NHR c )COO - , wherein R a is a C 1-18 hydrocarbon optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups, R b and R c are, independently of each other when considered separately, a hydrogen atom or a C 1-18 hydrocarbon optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups; or R a and R c together represent a C 3-11 alkanediyl optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide or alcohol groups.

3. The method according to claim 2, wherein R a is a C 1-8 hydrocarbyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups, R b is a hydrogen atom or a methyl group, and R c is a hydrogen atom or a C 1-8 hydrocarbyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups; or R a when combined with R c represents a C 3-8 alkanediyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide or alcohol groups.

4. The method according to any one of claims 2 to 3, wherein R a is phenyl, benzyl or a C 1-8 alkyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups, R b is a hydrogen atom, and R c is a hydrogen atom, phenyl, benzyl or a C 1-8 alkyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide, alcohol, hydroxyl, thioether, carboxylic acid groups; or R a and R c together represent a C 3-8 alkanediyl group optionally containing one or two functional groups selected from ether, ester, carbonyl, amine, amide or alcohol groups.

5. The method according to any one of claims 1 to 4, wherein the α - aminocarboxylate is selected from the group consisting of proline, valine, lysine, 2 - phenylglycine, phenylalanine, 2 - amino - 2 - methylpropanoic acid, and mixtures thereof, and the β - aminocarboxylate is anthranilate.

6. The method according to any one of claims 1 to 5, wherein 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 - tert - butylphenol, and mixtures thereof.

7. A method for rearranging an epoxide to an allylic alcohol, wherein the method is carried out in the presence of: i) a catalyst of the formula Zn(carboxylate)2; and ii) an aminophenol; wherein the molar ratio of the catalyst of the formula Zn(carboxylate)2 to the aminophenol is from 1:3 to 1:

5.

8. The method according to claim 7, wherein the carboxylate is selected from the group consisting of acetate, octanoate, 2 - ethylhexanoate, laurate, palmitate, stearate, 2 - octyldodecanoate, naphthenate, benzoate.

9. The method according to any one of claims 1 to 8, wherein the rearrangement of the epoxide to the allylic alcohol is carried out at a temperature of from 160 °C to 190 °C.

10. The method according to any one of claims 1 to 9, wherein the epoxide is limonene oxide and the allylic alcohol is carveol.

11. The method according to any one of claims 1 to 10, wherein the method further comprises the step of oxidizing the allylic alcohol obtained by the method defined in claims 1 to 6 or 7 to 9 to an α,β - unsaturated carbonyl compound.

12. The method according to claim 11, wherein the α,β - unsaturated carbonyl compound is carvone.

13. The method according to any one of claims 11 to 12, wherein the oxidation is carried out in the presence of a zirconium catalyst and a hydrogen acceptor.

14. The method according to claim 13, wherein the zirconium catalyst conforms to the following formula: [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’) wherein L is a bisphenolate, a triphenolate or a calixarene having at least 4 phenol 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, and 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 4 phenol units.

15. The method according to any one of claims 13 to 14, wherein the hydrogen acceptor is selected from the group consisting of benzaldehyde, cyclohexanone, 2-heptanone, 2-octanone, 2-pentanone, acetophenone, 4-methyl-2-pentanone, 3-methyl-2-butanone, isophorone, and mixtures thereof.

16. A catalytic system comprising or consisting of the following substances: i) A catalyst of the formula Zn(aa)2, where aa is an α-amino acid carboxylate having at least 3 carbon atoms; and ii) Aminophenol.

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