Process for preparing allyl alcohol

Abstract

The present invention relates to the field of organic synthesis, and more specifically to a method for the rearrangement of epoxides to allylic alcohols in the presence of a zinc catalyst and two aminophenols.

Description

[Technical Field]

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

[0002] Background technology Allyl alcohol represents a highly desirable skeleton that can be used as such or as a key intermediate for preparing more complex compounds in various fields, including fragrances, cosmetics, pharmaceuticals, and agricultural chemistry, among others. In particular, carveol is a valuable compound known as a fragrance component or an important intermediate for more complex compounds. Carveol can be obtained via rearrangement of limonene, i.e., limonene oxide prepared from renewable carbon sources, avoiding the use of petrochemical starting materials. Such access is particularly sought after today, with the increasing demand for products with environmentally friendly properties and reduced environmental and social impact. The rearrangement of epoxides to allyl alcohols has been disclosed in U.S. Patent No. 2003065230 and International Publication No. 2021151790, where such a rearrangement is carried out in the presence of a zinc catalyst and an activator. However, the reported conditions require temperatures of at least 200°C to achieve complete conversion and good yields. Such high temperatures are difficult to implement industrially and may require large amounts of energy. Furthermore, U.S. Patent No. 2003065230 and International Publication No. 2021151790 report a one-pot rearrangement of an epoxide to give an enone followed by oxidation. The oxidation is carried out in the presence of a hydrogen acceptor, sometimes called a sacrificial agent. The hydrogen acceptor is added incrementally, and the formed alcohol and unreacted hydrogen acceptor are then removed after each increment. The hydrogen acceptor or the corresponding alcohol are not recovered or recycled at the end of the process.

[0003] Therefore, there is a need today to develop sustainable methods that reduce energy consumption and waste generation.

[0004] The present invention enables the rearrangement of epoxides to allylic alcohols under catalytic conditions and at lower temperatures without compromising yield and while reducing the formation of by-products. Furthermore, the conditions of the present invention allow for the rearrangement of epoxides to allylic alcohols in the presence of a hydrogen acceptor under catalytic conditions in one pot, followed by oxidation under catalytic conditions to provide the desired compound in high yield with limited waste generation, and further allow for the recycling of the hydrogen acceptor or the corresponding alcohol. To our knowledge, none of the reported techniques combine these two steps to produce the corresponding α,β-unsaturated compound in one pot in high yield and in a sustainable manner.

[0005] Summary of the Invention The present invention relates to a novel method that allows for the preparation of allylic alcohols using renewable carbon-containing starting materials under mild conditions that have not previously been reported or suggested in the prior art.

[0006] Therefore, a first object of the present invention is a method for rearranging an epoxide to an allylic alcohol, said method comprising: i) a catalyst of the formula Zn(aa)2, where aa is an α-aminocarboxylate or β-aminocarboxylate having at least 3 carbon atoms; ii) in the presence of an aminophenol.

[0007] Another object of the present invention is a process for the rearrangement of an epoxide to an allylic alcohol, said process comprising the steps of: i) a catalyst represented by the formula Zn(carboxylate)2; ii) an aminophenol; is carried out in the presence of The molar ratio between the catalyst of formula Zn(carboxylate)2 and the aminophenol is comprised between 1:3 and 1:5.

[0008] A further object of the present invention is to i) a catalyst of the formula Zn(aa)2, where aa is an α-amino acid carboxylate or β-amino carboxylate having at least 3 carbon atoms; ii) an aminophenol; and

[0009] MODE FOR CARRYING OUT THE INVENTION Surprisingly, it has now been discovered that allylic alcohols can be prepared by rearranging epoxides in the presence of aminophenols using a zinc catalyst in a favorable manner. These unprecedented conditions allow for the production of α,β-unsaturated carbonyl compounds in very high yields without the need for high temperatures. Furthermore, the conditions of the present invention can be used in a one-step process in which the rearrangement of epoxides to allylic alcohols is followed by oxidation in the presence of a zirconium catalyst and a hydrogen acceptor. The one-pot process can be carried out at lower temperatures, allowing for a wider range of hydrogen acceptors, while avoiding the production of by-products and allowing for the recovery of the excess hydrogen acceptor and the reduced product, i.e., the corresponding alcohol.

[0010] Therefore, a first object of the present invention is a method for rearranging an epoxide to an allylic alcohol, said method comprising: iii) a catalyst of the formula Zn(aa)2, where aa is an α-aminocarboxylate or β-aminocarboxylate having at least 3 carbon atoms; iv) in the presence of an aminophenol.

[0011] For clarity, the phrase "α-aminocarboxylate having at least 3 carbon atoms" or similar phrases has the ordinary meaning as understood by those skilled in the art, i.e., R a , R b , and R c Compounds of formula R in which at least one group contains at least one carbon atom a R b C(NHR c )COO- In other words, the α-aminocarboxylate is a glycinate, i.e., CH2(NH2)COO - Unless otherwise specified, an α-aminocarboxylate is a carboxylate in which the carbon in the α-carboxylate is substituted with an amine functionality. An α-aminocarboxylate is an α-amino acid carboxylate. It is understood that orotic acid is not encompassed by the term "α-aminocarboxylate."

[0012] For clarity, the expression "β-aminocarboxylate" or similar expressions refers to the ordinary meaning understood by those skilled in the art, i.e., a carboxylate in which the carbon in β of the carboxylate is replaced by an amine functionality.

[0013] According to any embodiment of the present invention, the epoxide is represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof; In the formula, R 1 is a hydrogen atom or C 1-10 Alkyl group or C 2-10 is an alkenyl group, R 2 is a hydrogen atom or C 1-3 is an alkyl group, and R 3 is a hydrogen atom or C 1-5 is an alkyl group, or R 1 and R 3 are considered as a whole, and C 2-16 Alkanediyl group or C 3-16 represents an alkenediyl group, or R 2 and R 3 are considered as a whole, and C 2-16 represents an alkanediyl group, or R 1 and R 2 are considered as a whole, and C 2-16 Alkanediyl group or C 3-16 The compound is represented by the formula:

[0014] According to any embodiment of the present invention, the epoxide is represented by the formula [ka] in the form of any one of its stereoisomers or a mixture thereof; In the formula, R 1 is C 1-10 is an alkyl group, and R 2 is a hydrogen atom or C 1-3 is an alkyl group, and R 3 is C 1-3 is an alkyl group, or R 1 and R 3 are considered as a whole, and C 2-16 represents an alkanediyl group, or R 2 and R 3 are considered as a whole, and C 2-16 represents an alkanediyl group, or R 1 and R 2 are considered as a whole, and C 2-16 It is a compound represented by the formula:

[0015] According to any embodiment of the present invention, the allyl alcohol is [ka] in the form of any one of its stereoisomers or a mixture thereof, wherein R 1 , R 2 , and R 3 has the same meaning as defined above.

[0016] 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 1 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 single stereoisomer or a composition of matter comprising or consisting of various stereoisomers.

[0017] 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 (II) having the same chemical structure but differing in the configuration of the double bond.

[0018] According to any one 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 includes a composition of matter consisting of one or more compounds of formula (II) having the same chemical structure but differing in the configuration of double bonds.

[0019] 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.

[0020] According to any one of the above embodiments, R 1 is a hydrogen atom or C 1-8 Alkyl group or C 2-8 In particular, R 1 is a hydrogen atom or C 1-6 Alkyl group or C 2-6 In particular, R 1 is a hydrogen atom or C 1-4 Alkyl group or C 4-6 In particular, R 1 is a hydrogen atom or C 1-3 Alkyl group or C 4-6 In particular, R 1 is a hydrogen atom or C 1-3 Alkyl group or C 4-6 In particular, R 1 is a hydrogen atom or C 1-2 It can be an alkyl group or a C6 alkenyl group. More particularly, R 1 can be a hydrogen atom or methyl, ethyl, hex-3-en-1-yl or 4-methylpent-3-en-1-yl.

[0021] According to any one of the above embodiments, R 3is a hydrogen atom or C 1-5 In particular, R 3 is a hydrogen atom, C 1-3 It may be an alkyl group or a pentyl group. In particular, R 3 can be a hydrogen atom or a methyl, ethyl or pentyl group. In particular, R 3 may be a hydrogen atom or a pentyl group. More particularly, R 3 can be a hydrogen atom or a straight chain pentyl group.

[0022] According to any one of the above embodiments, R 2 is a hydrogen atom or C 1-2 In particular, R 2 may be a hydrogen atom or a methyl group. More particularly, R 2 can be a methyl group.

[0023] According to any one of the above embodiments, R 1 and R 2 are considered as a whole, and C 2-12 Alkanediyl or C 3-12 Represents an alkenediyl group. In particular, R 1 and R 2 are considered as a whole, and C 2-10 Alkanediyl group or C 3-10 Represents an alkenediyl group. In particular, R 1 and R 2 are considered as a whole, and C 2-8 Alkanediyl group or C 3-8 Represents an alkenediyl group. In particular, R 1 and R 2 are considered as a whole, and C 4-8 Alkanediyl group or C 4-8 Represents an alkenediyl group. In particular, R 1 and R 2 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 1 and R 2are 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.

[0024] According to any one of the above embodiments, R 2 and R 3 are considered as a whole, and C 2-12 Represents an alkanediyl group. In particular, R 2 and R 3 are considered as a whole, and C 2-10 Represents an alkanediyl group. In particular, R 2 and R 3 are considered as a whole, and C 2-8 Represents an alkanediyl group. In particular, R 2 and R 3 are considered as a whole, and C 4-8 Represents a glycandiyl group. In particular, R 2 and R 3 are considered as a whole, and C 6-8 represents an alkanediyl group. More particularly, R 2 and R 3 are considered together and the equation (a) [ka] in the form of any one of its stereoisomers or a mixture thereof.

[0025] According to any one of the above embodiments, R 1 and R 3 are considered as a whole, and C 2-12 Alkanediyl or C 3-12 Represents an alkenediyl group. In particular, R 1 and R 3 are considered as a whole, and C 2-10 Alkanediyl group or C 3-10 Represents an alkenediyl group. In particular, R 1 and R3 are considered as a whole, and C 2-8 Alkanediyl group or C 3-8 Represents an alkenediyl group. In particular, R 1 and R 3 are considered as a whole, and C 4-8 Alkanediyl group or C 4-8 Represents an alkenediyl group. In particular, R 1 and R 3 are considered as a whole, and C 5-8 Alkanediyl group or C 5-8 Represents an alkenediyl group. In particular, R 1 and R 3 are considered as a whole, and C 5-7 Alkanediyl group or C 5-7 Represents an alkenediyl group. In particular, R 1 and R 3 taken together represent a C6 alkanediyl group or a C6 alkenediyl group. More particularly, R 1 and R 3 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.

[0026] According to any one of the above embodiments, R 1 and R 3 is considered as one, C 2-12 Alkanediyl group or C 3-14 represents an alkenediyl group, and R 2 is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R 1 and R 3 are considered as a whole, and C 2-8 Alkanediyl group or C 4-12 represents an alkenediyl group, and R 2 is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R 1 and R3 are considered as a whole, and C 2-6 Alkanediyl group or C 4-10 represents an alkenediyl group, and R 2 is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R 1 and R 3 are considered as a whole, and C 2-4 Alkanediyl group or C 4-8 represents an alkenediyl group, and R 2 is a hydrogen atom or C 1-3 It is an alkyl group. In particular, R 1 and R 3 are considered as a whole, and C 2-4 Alkanediyl group or C 4-8 represents an alkenediyl group, and R 2 is a hydrogen atom or C 1-2 It is an alkyl group. In particular, R 1 and R 3 are considered as a whole, and C 2-3 Alkanediyl group or C 5-7 represents an alkenediyl group, and R 2 is a hydrogen atom or C 1-2 More particularly, R 1 and R 3 are taken together to represent a C3 alkanediyl group or a C6 alkenediyl group, and R 2 is a methyl group.

[0027] 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.

[0028] According to any one of the above embodiments of the invention, non-limiting examples of allyl alcohols 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]heptan-3-ol, (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol.

[0029] According to any embodiment of the present invention, the α-aminocarboxylate has at least 4 carbon atoms, preferably at least 5 carbon atoms, and even more preferably at least 6 carbon atoms.

[0030] According to any embodiment of the present invention, the α-aminocarboxylate is of formula R a R b C(NHR c )COO - wherein R a is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-18 is a hydrocarbon, and R b C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-18is a hydrocarbon, and R c is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-18 hydrocarbon or R a and R c When taken together, C optionally contains one or two functional groups selected from among an ether group, an ester group, a carbonyl group, an amine group, an amide group, or an alcohol group. 3-11 R represents an alkanediyl group. c C containing one or two carbonyl functional groups 1-18 In the case of hydrocarbons, the carbonyl functionality is not directly attached to NH.

[0031] By "...hydrocarbon group..." is meant that the group in question consists of hydrogen and carbon atoms and may be in the form of an aliphatic hydrocarbon, i.e., a linear or branched saturated hydrocarbon (e.g., an alkyl group), a linear or branched unsaturated hydrocarbon (e.g., an alkenyl or alkynyl group), a saturated cyclic hydrocarbon (e.g., a cycloalkyl), or an unsaturated cyclic hydrocarbon (e.g., a cycloalkenyl or cycloalkynyl), or an aromatic hydrocarbon, i.e., an aryl group, or may be in the form of a mixture of the aforementioned types of groups; for example, a particular group may contain linear alkyl, branched alkenyl (e.g., having one or more carbon-carbon double bonds), (poly)cycloalkyl, and aryl moieties, unless a specific limitation to only one type is mentioned. Similarly, in any embodiment of the present invention, when a group is referred to as being in the form of more than one type of topology (e.g., linear, cyclic, or branched) and / or saturated or unsaturated (e.g., alkyl, aromatic, or alkenyl), it also means that the group may contain moieties having any one of the topologies, or being saturated or unsaturated, as explained above. Similarly, in any embodiment of the present invention, when a group is referred to as being in one type of saturated or unsaturated form (e.g., alkyl), it means that the group can be of any type of topology (e.g., linear, cyclic, or branched) or can have some moieties with different topologies.

[0032] The term "hydrocarbon group optionally comprising" is understood to mean that the hydrocarbon group optionally comprises an alcohol, ketone, aldehyde, ether, ester, carboxylic acid, amine, amide, carbamate, or nitrile. These groups may replace a hydrogen atom of the hydrocarbon group and thus be laterally attached to the hydrocarbon, or may replace a carbon atom (if chemically possible) of the hydrocarbon group and thus be inserted into the hydrocarbon chain. For example, the -CH2-CH2-CHOH-CH2- group represents a C4 hydrocarbon group containing an alcohol group (substitution of a hydrogen atom), and similarly, the -CH2-CH2-O-CH2-CH2-O-CH2-CH2- group represents a C6 hydrocarbon group containing two ether groups (substitution of a carbon atom / insertion into the hydrocarbon chain).

[0033] The term "optionally" is understood to mean that a group may or may not include certain functional groups or substituents.

[0034] According to any embodiment of the present invention, R a C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-15 It may be a hydrocarbon. In particular, R a C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-12 It may be a hydrocarbon group. In particular, R a C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-10 It may be a hydrocarbon group. In particular, R a C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-8It may be a hydrocarbon group. In particular, R a is a phenyl group, a benzyl group, or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-8 More particularly, R a is a phenyl group, a benzyl group, or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-6 It may be an alkyl group.

[0035] According to any embodiment of the present invention, R b is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-15 It may be a hydrocarbon. In particular, R b is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-12 It may be a hydrocarbon group. In particular, R b is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-10 It may be a hydrocarbon group. In particular, R b is a hydrogen atom or optionally contains one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-8 It may be a hydrocarbon group. In particular, R bis a hydrogen atom or optionally contains one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-8 In particular, R b is a hydrogen atom, or C 1-6 In particular, R b is a hydrogen atom, or C 1-4 In particular, R b is a hydrogen atom, or C 1-3 In particular, R b is a hydrogen atom, or C 1-2 In particular, R b may be a hydrogen atom or a methyl group. More particularly, R b can be a hydrogen atom.

[0036] According to any embodiment of the present invention, R c is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-15 It may be a hydrocarbon. In particular, R c is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-12 It may be a hydrocarbon group. In particular, R c is a hydrogen atom or C optionally containing one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-10 It may be a hydrocarbon group. In particular, R c is a hydrogen atom or optionally contains one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group;1-8 It may be a hydrocarbon group. In particular, R c is a C which contains one or two functional groups selected from a hydrogen atom, a phenyl group, a benzyl group, or an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group, as desired; 1-8 In particular, R c is a hydrogen atom or optionally contains one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; 1-8 In particular, R c is a hydrogen atom, or C 1-6 In particular, R c is a hydrogen atom, or C 1-4 In particular, R c is a hydrogen atom, or C 1-3 In particular, R c is a hydrogen atom, or C 1-2 In particular, R c may be a hydrogen atom or a methyl group. More particularly, R c can be a hydrogen atom.

[0037] According to any embodiment of the present invention, R a and R c When taken together, C optionally contains one or two functional groups selected from among an ether group, an ester group, a carbonyl group, an amine group, an amide group, or an alcohol group. 3-10 In particular, R a and R c When taken together, C optionally contains one or two functional groups selected from among an ether group, an ester group, a carbonyl group, an amine group, an amide group, or an alcohol group. 3-8 In particular, R a and R c When considered together, C 3-6In particular, R a and R c When considered together, C 4-6 It may be an alkanediyl group. Even more particularly, R a and R c When considered together, C 5-6 It may be an alkanediyl group.

[0038] According to any embodiment of the present invention, the α-aminocarboxylate has from 4 to 10 carbon atoms.

[0039] According to any embodiment of the present invention, the α-aminocarboxylates may be different or the same.

[0040] According to any embodiment of the present invention, the α-aminocarboxylate may be derived from an α-amino acid of natural or artificial origin, and may be a natural α-amino acid, 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 and R c are considered as one, =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 norleucine [R a =(CH2)3CH 3; R b and R c =H], norvaline [R a =(CH2)2CH 3; 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 =CH2CH 3; R b and R c =H), 2-amino-2-methylpropanoic acid Ra and R b =CH 3; R c =H), and homoserine [R a =(CH2)2OH ; R b and R c =H]. In particular, the α-amino carboxylate may be derived from an α-amino acid that may be selected from the group consisting of proline, valine, lysine, 2-phenylglycine, phenylalanine, 2-amino-2-methylpropanoic acid, and mixtures thereof.

[0041] According to any embodiment of the present invention, the β-aminocarboxylate is an anthralinate.

[0042] 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.

[0043] Alternatively, the process of the invention for rearranging an epoxide to an allylic alcohol can be carried out in the presence of a catalyst of formula Zn(carboxylate)2. Therefore, another object of the invention is a process for rearranging an epoxide to an allylic alcohol, said process comprising: i) a catalyst represented by the formula Zn(carboxylate)2; ii) an aminophenol; is carried out in the presence of The molar ratio between the catalyst of formula Zn(carboxylate)2 and the aminophenol is comprised between 1:3 and 1:5.

[0044] The term "carboxylate" is understood as a ligand containing a COO functional group. In particular, a carboxylate is a ligand of the formula R d COO, wherein R d is C 1-18 Alkyl group or C 6-10 Aryl groups, especially C 1-16 The carboxylate may be selected from the group consisting of acetate, octoate, 2-ethyl-hexanoate, laurate, palmitate, stearate, 2-octyldodecanoate, benzoate, naphthenate.

[0045] The term "aryl group" has its usual meaning in the art, i.e., an aromatic hydrocarbon group such as an optionally substituted phenyl 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.

[0046] According to any one of the embodiments of the present invention, the catalyst represented by the formula Zn(carboxylate)2 and the aminophenol are comprised between 1:3 and 1:4.

[0047] According to any one of the embodiments of the present invention, epoxide, allylic alcohol, and aminophenol have the same meaning as defined above.

[0048] 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.

[0049] The catalyst of formula Zn(aa)2 is a commercially available compound or can be prepared by several methods, such as that reported in Polymers (Basel, Switzerland) (2019), 11(5), 790. Alternatively, the catalyst of formula Zn(aa)2 can be formed in situ by the reaction of ZnO with two equivalents of AA.

[0050] The catalysts of formula Zn(carboxylate)2 are commercially available compounds or can be prepared by several methods, such as those reported in Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (2008), 70A(1), 217. Alternatively, the catalysts of formula Zn(carboxylate)2 are formed in situ by the reaction of ZnO with two equivalents of carboxylic acid.

[0051] The aminophenol can be added to the reaction medium of the method 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 1 mol% to 5 mol%, or even 1 mol% to 3 mol%, relative to the amount of epoxide. It goes without saying that the method 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.

[0052] 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 160° C. and 190° C. In particular, the temperature ranges 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.

[0053] 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 These include aromatic solvents, hydrocarbon solvents such as limonene, decane, dodecane, or heavier solvents, 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.

[0054] 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.

[0055] The process of the present invention for the rearrangement of an epoxide to an allylic alcohol can be carried out under atmospheric pressure.

[0056] According to an optional embodiment of the present invention, the process of the present invention further comprises a step of oxidizing the allylic alcohol obtained after the process as defined above to an α,β-unsaturated carbonyl compound.

[0057] According to any embodiment of the present invention, the α,β-unsaturated carbonyl compound has the formula [ka] in the form of any one of its stereoisomers or a mixture thereof, wherein R 1 , R 2 , and R 3 have the same meaning as defined above.

[0058] According to any embodiment of the present invention, the α,β-unsaturated carbonyl compound is carvone.

[0059] According to an optional embodiment of the present invention, the oxidation is carried out in the presence of a zirconium catalyst and a hydrogen acceptor.

[0060] According to any embodiment of the present invention, the zirconium catalyst comprises: formula [Zr(L)(X) r ](IV) or [Zr(L') p (X) n ](IV') 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.

[0061] 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.

[0062] According to any embodiment of the present invention, the bisphenolate may 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).

[0063] According to any embodiment of the present invention, the anionic ligands may be, independently of one another, halogen atoms, β-diketonates, OOCR 7 group, or OR 8 is a group, wherein R 7 C 1-10 alkyl group, benzyl group, naphthyl group, or phenyl group optionally substituted with a hydroxy group; R 8 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 9- C(=O)-CH=C(O-)-R 10 wherein R 9 and R 10 are independent of each other, C 1-6 Alkyl groups, especially C 1-4 The 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 7 is C 1-8 Alkyl groups, especially C 1-6 Alkyl groups, more particularly C 1-5 In particular, R 8 is C 1-4 The anionic ligand 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 acetylacetonates.

[0064] According to a particular embodiment, when p is 0 and n is 4, X is of formula OR as defined above. 9 It is an alkoxide represented by the formula:

[0065] According to an optional embodiment of the present invention, the catalyst represented by formula (IV) 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 cation exchangeable ...

[0066] The catalyst represented by formula (IV) or (IV') 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.

[0067] 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.

[0068] 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.

[0069] 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.

[0070] 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 O 4 solvents 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.

[0071] 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.

[0072] 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.

[0073] 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.

[0074] Another object of the present invention is to provide i) a catalyst of the formula Zn(aa)2, where aa is an α-amino acid carboxylate or β-amino carboxylate having at least 3 carbon atoms; ii) an aminophenol; and

[0075] According to any embodiment of the present invention, the catalyst system as defined above is suitable for use in a process for rearranging an epoxide to an allylic alcohol as defined above.

[0076] Another object of the present invention is to provide a process for the rearrangement of an epoxide to an allylic alcohol, comprising the steps of: i) a catalyst of the formula Zn(aa)2, where aa is an α-amino acid carboxylate or β-amino carboxylate having at least 3 carbon atoms; ii) an aminophenol; The use of a catalyst system comprising or consisting of:

[0077] Typical modes for carrying out the method of the invention are reported below in the Examples.

[0078] 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 of all compounds prepared conforms to NMR reported in the literature.

[0079] Example 1 Rearrangement of 1,2-limonene oxide to carveol using present and comparative conditions A mixture of 1,2-limonene oxide (60% cis isomer and 40% trans isomer), Zn catalyst, and 2-aminophenol (2-AP) (the AP / Zn equivalent ratio is specified in Table I) was heated to 185 °C in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. The internal temperature was maintained at 185 °C for the entire reaction duration. The crude product was then flash distilled to determine the amount of residue formed during the reaction, and the yield was calculated based on the GC purity of the distilled product. The conversion, selectivity (sum of carveol and carvone / conversion), and isolated yield are reported in Table 1.

[0080] [Table 1]

[0081] 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 >99 GC% R-(-)-carvone.

[0082] 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%.

[0083] 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 R-(-)-carvone with a purity of >99GC%.

[0084] 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%.

[0085] 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% zirconium(propoxide)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. After rectification, the excess of benzaldehyde and the co-produced benzyl alcohol were recovered separately in 95% overall yield and greater than 99% purity, giving R-(-)-carvone in 98% yield and greater than 99% GC% purity.

[0086] Example 7 3,8,8-trimethyl-4-oxatricyclo[5.1.0.0] using the conditions of the present invention 3,5 Rearrangement of ]octane to 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol 3,8,8-trimethyl-4-oxatricyclo[5.1.0.0 3,5 A mixture of 1,2-dimethyl-2,3-octane (5 g, 32 mmol), Zn(L-prolinate)2 (0.25 mol%), and 2-aminophenol (4 equiv. / Zn) was heated at 185 °C for 5 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser to complete the conversion. After distillation of the residue, the product was obtained in 85% yield 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.

[0087] Example 8 Rearrangement of α-pinene oxide to 6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-ol using the conditions of the present invention A mixture of α-pinene oxide (5 g, 32 mmol), Zn(L-prolinate)2 (1 mol%), and 2-aminophenol (3 equiv. / Zn) was heated in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser at 190 °C for 7 h to give 80% GC conversion of 2-methylenebicyclo[3.1.1]heptan-3-ol with 75% GC selectivity.

[0088] Example 9 Rearrangement of β-pinene oxide epoxide to (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol using the conditions of the present invention A mixture of Zn(phenylglycinate)2 (60 mg, 0.16 mmol) and 2-aminophenol (4 equiv. / Zn) in 1,3-diisopropylbenzene (2 mL) was heated at 180 °C for 1 h in a Schlenk vessel equipped with a magnetic stirrer, thermometer, and condenser. β-Pinene oxide (5 g, 32 mmol) was then slowly added and heated for 6 h to a conversion of 72% GC. (6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol was obtained with a selectivity of 63% GC.

[0089] Example 10 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 (LMO, 60% cis isomer and 40% trans isomer, 400 g), catalyst, and 2-aminophenol (2-AP) (the equivalents of 2-AP relative to Zn are specified in Table 2) was heated to the temperatures specified in Table 2 in a glass reactor equipped with a stirrer, thermometer, Dean-Stark trap, and condenser. The temperature was maintained until the conversion of R-LMO was greater than 96%. After cooling, the oxidation catalyst was added along with the hydrogen acceptor (amount specified in Table 2). 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, the time column is omitted. When a reaction mixture is reported as 2 / 2, 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, followed by a repeat of the procedure. For example, 2 / 2 / 2 means that HA was added three times, every 2 hours. The crude carvone was then purified by distillation to obtain carvone with a purity of >98%. The yield is reported in the carvone isolation yield column. Separately or together, the excess 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.

[0090] Table 2. Rearrangement of 1,2-limonene oxide to carveol followed by oxidation and Oppenauer oxidation to give R-(-)-carvone in one pot using the present and comparative conditions. [Table 2] 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 for invention 5) 2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol] 6) 1,2-Limonene oxide

[0091] 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 the rearrangement of an epoxide to an allylic alcohol, the process comprising: i) Formula Zn(aa) ２ wherein aa is an α-aminocarboxylate or β-aminocarboxylate having at least 3 carbon atoms; ii) A process carried out in the presence of an aminophenol.

2. The α-aminocarboxylate is represented by the formula R ａ R ｂ C (NHR ｃ ) COO － wherein R ａ C may optionally contain one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group. １－１８ is a hydrocarbon, and R ｂ and R ｃ are, when considered separately, independently of one another, a hydrogen atom or optionally contain one or two functional groups selected from among an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, a carboxylic acid group; １－１８ hydrocarbon or R ａ and R ｃ When taken together, C may optionally contain one or two functional groups selected from ether, ester, carbonyl, amine, amide, or alcohol groups. ３－１１ The method of claim 1 , wherein the alkanediyl group is an alkanediyl group.

3. R ａ C may optionally contain one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group. １－８ is a hydrocarbon group, R ｂ is a hydrogen atom or a methyl group, and R ｃ C may contain a hydrogen atom or one or two functional groups selected from an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group. １－８ a hydrocarbon group, or R ａ and R ｃ When taken together, C may optionally contain one or two functional groups selected from ether, ester, carbonyl, amine, amide, or alcohol groups. ３－８ The method of claim 2 , wherein the alkanediyl group is an alkanediyl group.

4. R ａ C may contain one or two functional groups selected from a phenyl group, a benzyl group, or an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group. １－８ is an alkyl group, and R ｂ is a hydrogen atom, and R ｃ may contain one or two functional groups selected from a hydrogen atom, a phenyl group, a benzyl group, or an ether group, an ester group, a carbonyl group, an amine group, an amide group, an alcohol group, a hydroxy group, a thioether group, and a carboxylic acid group; １－８ alkyl group or R ａ and R ｃ When taken together, C may optionally contain one or two functional groups selected from ether, ester, carbonyl, amine, amide, or alcohol groups. ３－８ 4. The method according to claim 2 or 3, wherein the alkanediyl group is an alkanediyl group.

5. 5. The method of 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 an anthranilate.

6. 6. The method of 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-tertbutylphenol, and mixtures thereof.

7. 1. A process for rearranging an epoxide to an allylic alcohol, the process comprising: i) Formula Zn(carboxylate) ２ A catalyst represented by ii) an aminophenol; and is carried out in the presence of Formula Zn(carboxylate) ２ and the aminophenol is in a molar ratio of 1:3 to 1:

5.

8. 8. The method of claim 7, wherein the carboxylate is selected from the group consisting of acetate, octoate, 2-ethyl-hexanoate, laurate, palmitate, stearate, 2-octyldodecanoate, naphthenate, benzoate.

9. A process according to any one of claims 1 to 8, wherein the process for rearrangement of epoxides to allylic alcohols is carried out at a temperature comprised between 160°C and 190°C.

10. 10. The method of any one of claims 1 to 9, wherein the epoxide is 1,2-limonene oxide and the allyl alcohol is carveol.

11. The method according to any one of claims 1 to 10, further comprising a step of oxidizing the allyl alcohol obtained according to the method of claims 1 to 6 or 7 to 9 to an α,β-unsaturated carbonyl compound.

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

13. 13. The method of claim 11, wherein the oxidation is carried out in the presence of a zirconium catalyst and a hydrogen acceptor.

14. The zirconium catalyst is formula [Zr(L)(X) ｒ ] (I) or [Zr(L') ｐ (X) ｎ ](I′) 14. The method of claim 13, 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.

15. 15. The method of claim 13 or 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. 1. A catalyst system comprising: i) Formula Zn(aa) ２ wherein aa is an α-amino acid carboxylate having at least 3 carbon atoms; ii) an aminophenol; and

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