Intra-ring double bond isomerization method

Abstract

The invention relates to the field of organic synthesis. The present invention relates to a process for the preparation of 1-(cycloalkane-1-en-1-yl) acyl derivatives, and more specifically, to a process for the preparation of 1-(cycloalkane-1-en-1-yl) acyl derivatives or 1-(cycloalkene-1-yl) acyl derivatives comprising the isomerization of carbon-carbon double bonds in the conjugated ring in the presence of a catalyst system comprising palladium (Pd) and molecular hydrogen or a hydrogen source.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis. More specifically, it relates to a method for preparing 1-(cycloalkane-1-ene-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivatives, which comprises isomerizing a conjugated intracyclic carbon-carbon double bond in the presence of a catalyst system comprising palladium (Pd) and molecular hydrogen or a hydrogen source. Background Art

[0002] Many 1-(cycloalkane-1-ene-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivatives defined in formula (I) are useful products themselves, or are useful intermediates for preparing other important raw materials. The compounds of formula (I) are particularly useful for the perfume industry, especially 1-(3,3-dimethylcyclohex-1-ene-1-yl)ethan-1-one, which is used to prepare industrially related compounds (such as The preparation of 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivatives mostly results in undesirable regioisomers or regioisomer mixtures in which the double bond is not in the correct position and a supplementary isomerization reaction is required. However, the isomerization reaction of the conjugated intracyclic carbon-carbon double bond to give 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivatives has not been reported. Therefore, it is necessary to develop such isomerization reactions.

[0003] The invention obtains 1-(cycloalkane-1-ene-1-yl) acyl or 1-(cycloalkadien-1-yl) acyl derivatives with high selectivity by intramolecular double bond isomerization in the presence of a catalyst system comprising palladium (Pd) and molecular hydrogen or a hydrogen source. Summary of the invention

[0004] We have now found that 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivatives can be produced in an advantageous manner by means of the catalytic isomerization described and that this results in minimal by-product formation and high productivity.

[0005] Therefore, a first object of the present invention is a process for preparing 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivatives comprising isomerization of an intracyclic carbon-carbon double bond, wherein the isomerization is carried out by contacting a substrate comprising conjugated intracyclic carbon-carbon double bonds with a catalyst system comprising:

[0006] i) palladium (Pd); and

[0007] ii) Molecular hydrogen or a source of hydrogen.

[0008] For the sake of clarity, it should be understood that the expression "hydrogen source" means a source that is generally understood in the art, i.e., a source that is capable of producing molecular hydrogen (i.e., H 2 ), hydrogen atoms or their equivalents.

[0009] For the sake of clarity, it should be understood that the expression "conjugated endocyclic carbon-carbon double bond" is intended to have the usual meaning in the art, ie the substrate comprises at least one double bond which is conjugated to the acyl functional group.

[0010] According to any embodiment of the present invention, the 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivative is a compound of the formula:

[0011]

[0012] The compound is in the form of any stereoisomer or a mixture thereof, wherein one dotted line is a carbon-carbon single bond and the other is a carbon-carbon single bond or a carbon-carbon double bond; m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

[0013] According to any embodiment of the present invention, the substrate is a compound of the formula:

[0014]

[0015] The compound is in the form of any stereoisomer or a mixture thereof, wherein one dotted line is a carbon-carbon single bond and the other is a carbon-carbon single bond or a carbon-carbon double bond; m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

[0016] According to any embodiment of the present invention, the 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivative is a compound of the formula:

[0017]

[0018] The compound is in the form of any stereoisomer or a mixture thereof, wherein one dotted line is a carbon-carbon single bond and the other is a carbon-carbon single bond or a carbon-carbon double bond; m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

[0019] According to any embodiment of the present invention, the substrate is a compound of the formula:

[0020]

[0021] The compound is in the form of any stereoisomer or a mixture thereof, wherein one dotted line is a carbon-carbon single bond and the other is a carbon-carbon single bond or a carbon-carbon double bond; m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

[0022] For the sake of clarity, by expressing "any stereoisomer thereof or a mixture thereof" or similar expressions, it is meant the common meaning understood by those skilled in the art, that is, the compounds of formula (I) and formula (II) can be pure enantiomers, or a mixture of multiple enantiomers. In other words, the compound of formula (I) or the compound of formula (II) can have multiple stereo centers, and each of the stereo centers can have two different stereochemicals (e.g., R or S). The compound of formula (I) or the compound of formula (II) can even be in the form of a pure enantiomer, or in the form of a mixture of multiple enantiomers. The compound of formula (I) or the compound of formula (II) can be a racemic form or a non-racemic (scalemic) form. Therefore, the compound of formula (I) or the compound of formula (II) can be a stereoisomer, or in the form of a material composition comprising various stereoisomers or consisting of various stereoisomers.

[0023] For the sake of clarity, by stating that "one dotted line is a carbon-carbon single bond and the other dotted line is a carbon-carbon single bond or a carbon-carbon double bond" or similar statements, it is meant to be understood by those skilled in the art as having the normal meaning that the entire bond (solid and dotted) between the carbon atoms connected by the dotted lines is a carbon-carbon single bond or a double bond. In other words, the compounds of formula (I) and (II) are cycloalkenyl or cycloalkadienyl derivatives. Those skilled in the art are fully aware that when one dotted line is a carbon-carbon double bond, the adjacent dotted line cannot be a double bond. In other words, the compound of formula (I) may be a 1-(cycloalkene-1-yl)acyl group of formula (Ia), or a 1-(cycloalkadien-1-yl)acyl group of formula (Ib):

[0024]

[0025] The compound is in the form of any stereoisomer or a mixture thereof, wherein m, n, R 1 and R 2 has the same meaning as defined above,

[0026] and

[0027] The compound of formula (II) may conform to formula (IIa) or (IIb):

[0028]

[0029] The compound is in the form of any stereoisomer or a mixture thereof, wherein m, n, R 1 and R 2 has the same meaning as defined above.

[0030] The terms "alkyl", "alkoxy" and "alkenyl" are understood to include branched and straight chain alkyl, alkoxy and alkenyl groups. The term "alkenyl" or "cycloalkenyl" is understood to include one olefinic double bond. The term "cycloalkyl" or "cycloalkenyl" is understood to include monocyclic groups.

[0031] For the sake of clarity, by stating “R 2 "Represents a substituent on a ring" or similar expressions refer to the normal meaning understood by those skilled in the art, that is, the group is bonded to the ring at any available position.

[0032] The term "optionally / optionally / depending on the situation (optionally)" is understood to mean that a certain group to be optionally substituted may or may not be substituted with a certain functional group. The term "one or more" is understood to mean substituted with 1 to 7, preferably 1 to 5, preferably 1 to 3, more preferably 1 to 2 certain functional groups.

[0033] For the sake of clarity, by stating that “two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 "Cycloalkenyl" means that the carbon atoms to which the two groups are bonded are included in the C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl.

[0034] According to any embodiment of the present invention, when the substrate is a compound of formula (IIb), the result of the isomerization is the preparation of a 1-(cyclodien-1-yl)acyl derivative of formula (Ib), or the result is a composition of matter comprising at least 50% of a 1-(cyclodien-1-yl)acyl derivative of formula (Ib) and at most 50% of a 1-(cyclodien-1-yl)acyl derivative of formula (A):

[0035]

[0036] The compound is in the form of any stereoisomer or a mixture thereof, wherein m, n, R 1 and R 2 has the same meaning as defined above.

[0037] According to any embodiment of the invention, the dashed line is a single bond.

[0038] According to any embodiment of the present invention, the 1-(cycloalkane-1-en-1-yl)acyl derivative is a compound of the formula:

[0039]

[0040] The compound is in the form of any stereoisomer or a mixture thereof, wherein m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

[0041] According to any embodiment of the present invention, the substrate is a compound of the formula:

[0042]

[0043] The compound is in the form of any stereoisomer or a mixture thereof, wherein m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

[0044] According to any embodiment of the present invention, the compound of formula (II) is different from the compound of formula (I); that is, R 2The group makes the compound of formula (II) different from the compound of formula (I), in particular, the compound of formula (II') is different from the compound of formula (I'); that is, R 2 The group is such that the compound of formula (IIa) is not the compound of formula (Ia), and even more particularly, the compound of formula (IIa) is different from the compound of formula (Ia); that is, R 2 The group is such that the compound of formula (IIa) is not a compound of formula (Ia).

[0045] According to any embodiment of the present invention, the compounds of formula (II), (II') or (IIa) and the compounds of formula (I), (I') or (Ia) may contain at least one R at the 2, 3, 5 or 6 position or at the 2, 3, 4 or 5 position. 2 In particular, the compounds of formula (II), (II') or (IIa) and the compounds of formula (I), (I') or (Ia) may contain at least one R at position 3 or 5 or at position 4 or 5. 2 In particular, the compounds of formula (II), (II') or (IIa) and the compounds of formula (I), (I') or (Ia) may contain at least one R at the 5 position. 2 Even more particularly, the compounds of formula (II), (II') or (IIa) and the compounds of formula (I), (I') or (Ia) may contain at least two R 2 Group.

[0046] According to any embodiment of the present invention, m may be an integer from 0 to 5. In particular, m may be an integer from 0 to 3. In particular, m may be an integer from 0 to 2. In particular, m may be 0 or 1. Even more particularly, m may be 1.

[0047] According to any embodiment of the present invention, R 2 Simultaneously or independently, it can be C 1-4 Alkyl or C 2-4 Alkenyl; or two R 2 The groups combine to form C 5-6 Cycloalkyl, optionally substituted with one or more C 1-4 Alkyl, C 2-4 Alkenyl or C 1-4 In particular, R 2 Simultaneously or independently, it can be C 1-3 Alkyl or C 2-4 Alkenyl; or two R 2 The groups combine to form C 5-6 Cycloalkyl, substituted with one or more C 1-3 Alkyl, C 2-3 Alkenyl or C 1-3 In particular, R 2 Simultaneously or independently, it can be C1-3 Alkyl or C 2-4 Alkenyl; or two R 2 The groups combine to form C 5-6 Cycloalkyl, substituted with one or more C 1-2 Alkyl or C 1-2 In particular, R 2 Simultaneously or independently, it can be C 1-3 Alkyl; or two R 2 The groups combine to form C 5-6 In particular, R 2 At the same time or independently, they may be methyl or ethyl. More particularly, R 2 It may be methyl.

[0048] According to any embodiment of the present invention, n may be an integer from 1 to 6, or even an integer from 1 to 4, or even an integer from 1 to 3, or even an integer from 1 to 2. In particular, n may be 1 or 2 or 3. Even more particularly, n may be 2.

[0049] According to any embodiment of the present invention, the compound of formula (I) is a compound of the formula:

[0050]

[0051] The compound is in the form of any stereoisomer or a mixture thereof, wherein p is 0 or 1; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 Each independently represents a hydrogen atom, C 1-6 Alkyl or C 2-6 alkenyl; or R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 The two groups in the 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; or R3 and R 1 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; or R 4 and R 1 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; provided that R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 Such that the compound of formula (III) is different from the compound of formula (IV) as defined below.

[0052] And the compound of formula (II) conforms to the following formula:

[0053]

[0054] The compound is in the form of any stereoisomer or a mixture thereof, wherein p, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 has the same meaning as defined above.

[0055] According to any embodiment of the present invention, the compound of formula (III) is different from the compound of formula (IV). In other words, the compound of formula (III) is different from the compound of formula (IV)

[0056] According to any embodiment of the present invention, p is 1. In other words, the compound of formula (III) is a compound of the formula:

[0057]

[0058] The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C1-6 Alkoxy; each R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 Each independently represents a hydrogen atom, C 1-6 Alkyl or C 2-6 alkenyl; or R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 The two groups in the 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; or R 3 and R 1 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; or R 4 and R 1 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; provided that R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 Such that the compound of formula (V) is different from the compound of formula (VI) as defined below.

[0059] The compound of formula (IV) conforms to the following formula:

[0060]

[0061] The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 , R3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 has the same meaning as defined above.

[0062] According to any embodiment of the present invention, the compound of formula (V) is different from the compound of formula (VI). In other words, the compound of formula (V) is different from the compound of formula (VI).

[0063] According to any embodiment of the present invention, R 4 , R 3 , R 10 and R 9 At least one of the groups is not a hydrogen atom, and excludes the following compounds of formula (III) or formula (V), wherein R 3 With R 10 Same, R 4 With R 9 Same, R 5 With R 8 The same. In particular, R 4 and R 9 At least one of the groups is not a hydrogen atom.

[0064] According to any embodiment of the present invention, R 3 , R 4 , R 5 , R 7 and R 10 Independently of each other, they can represent hydrogen atoms, C 1-4 Alkyl or C 2-4 In particular, R 3 , R 4 , R 5 , R 7 and R 10 Independently of each other, they can represent hydrogen atoms or C 1-3 In particular, R 3 , R 4 , R 5 , R 7 and R 10 Independently of each other, they can represent hydrogen atoms or C 1-2 Alkyl. Even more particularly, R 3 , R 4 , R 5 , R 7 and R 10 Can represent a hydrogen atom.

[0065] According to any embodiment of the present invention, the compound of formula (V) is a compound of the following formula:

[0066]

[0067] The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; each R 6 , R 8 and R 9 Each independently represents a hydrogen atom, C 1-6 Alkyl or C 2-6 alkenyl; or R 8 and R 9 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy;

[0068] And the compound of formula (VI) conforms to the following formula:

[0069]

[0070] The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 , R 6 , R 8 and R 9 has the same meaning as defined above.

[0071] According to any embodiment of the present invention, R 9 , R 8 and R 6 At least one of the groups is not a hydrogen atom.

[0072] According to any embodiment of the present invention, R 6 Can represent hydrogen atoms, C 1-4 Alkyl or C 2-4 In particular, R 6 Can represent hydrogen atoms or C 1-3 In particular, R 6 Can represent hydrogen atoms or C 1-2 In particular, R 6 may represent a hydrogen atom or a methyl group. Even more particularly, R 6 Can represent a hydrogen atom.

[0073] According to any embodiment of the invention, the compound of formula (VII) is different from the compound of formula (VIII).

[0074] According to any embodiment of the present invention, the compound of formula (VII) is a compound of the formula:

[0075]

[0076] The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; each R 8 and R 9 Each independently represents a hydrogen atom, C 1-6 Alkyl or C 2-6 alkenyl; or R 8 and R 9 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy;

[0077] And the compound of formula (VIII) conforms to the following formula:

[0078]

[0079] The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 , R 8 and R 9 has the same meaning as defined above.

[0080] According to any embodiment of the present invention, R 9 and R 8 At least one of the groups is not a hydrogen atom.

[0081] According to any embodiment of the present invention, R 8 Can represent hydrogen atoms, C 1-4 Alkyl or C 2-4 In particular, R 8 Can represent hydrogen atoms, C 1-3 Alkyl or C 2-3 In particular, R 8 Can represent hydrogen atoms or C 1-2 Alkyl. Even more specifically, R 8 Can represent methyl.

[0082] According to any embodiment of the present invention, R 9 Can represent hydrogen atoms, C 1-4 Alkyl or C 2-4 In particular, R 9 Can represent hydrogen atoms, C 1-3 Alkyl or C 2-3 In particular, R 9 Can represent hydrogen atoms or C 1-2 Alkyl. Even more specifically, R 9 Can represent methyl.

[0083] According to any embodiment of the present invention, R 1 Can be C 1-4 Alkyl, C 2-4 Alkenyl or C 1-4 In particular, R 1 Can be C 1-3 Alkyl, C 2-3 Alkenyl or C 1-3 In particular, R 1 Can be C 1-3 In particular, R 1 It may be methyl, ethyl or propyl. Even more particularly, R 1 It may be methyl.

[0084] Non-limiting examples of suitable compounds of formula (I) may include 1-(5,5-dimethylcyclohex-1-en-1-yl)ethan-1-one, 1-(5-ethyl-5-methylcyclohex-1-en-1-yl)ethan-1-one, 1-(5,5-dimethylcyclohexa-1,3-dien-1-yl)ethan-1-one, 1-(4,5,5-trimethylcyclohex-1-en-1-yl)ethan-1-one, and 1-(4-isopropyl-4-methylcyclopent-1-en-1-yl)ethan-1-one.

[0085] Non-limiting examples of suitable compounds of formula (II) may include 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one, 1-(3-ethyl-3-methylcyclohex-1-en-1-yl)ethan-1-one, 1-(3,3-dimethylcyclohex-1,4-dien-1-yl)ethan-1-one, 1-(3,3,4-trimethylcyclohex-1-en-1-yl)ethan-1-one, and 1-(3-isopropyl-3-methylcyclopent-1-en-1-yl)ethan-1-one.

[0086] According to any embodiment of the present invention, the catalyst system comprises palladium (Pd) in the form of a homogeneous complex or in the form of an elemental metal. In particular, the catalyst system comprises palladium (Pd) in the form of an elemental metal. Suitable forms of such metals for carrying out the chemical reaction are well known to those skilled in the art.

[0087] According to any of the above embodiments of the present invention, the palladium (Pd) is supported on a support material.

[0088] For the sake of clarity, support material refers to a material upon which the metal can be deposited and which is inert to the hydrogen source and substrate.

[0089] According to any of the above embodiments of the present invention, specific and non-limiting examples of support materials are carbon, silica or alumina, and such supports are well known to those skilled in the art.

[0090] Supported palladium (Pd) is a known compound and is commercially available. A person skilled in the art is able to select the preferred metal species depending on the way the metal is deposited on the support, the ratio of the metal on the support material, the form (powder, granules, pellets, extrudates, foams, ...) and the surface area of ​​the support.

[0091] According to any of the above embodiments of the invention, the amount of metal relative to the support may range from 0.05% to 25% w / w, or even from 1% to 6% w / w, relative to the weight of the support used.

[0092] Palladium (Pd) in supported form or as is can be added to the reaction medium of the process of the invention in a wide range of concentrations. As non-limiting examples, metal concentration values ​​ranging from 0.01 mol% to 10 mol% relative to the total amount of substrate can be cited. Preferably, the metal concentration is from 0.02 mol% to 5 mol%, or even from 0.04 mol% to 2 mol%. It goes without saying that, as is known to those skilled in the art, the optimal concentration of the metal will depend on the nature of the substrate, the nature of the substrate, whether the process is operated batchwise or continuously, the temperature and H used in the process. 2 Pressure and the time it takes to react.

[0093] The supported palladium can be recycled at the end of the process of the invention. In other words, the supported palladium can be recovered at the end of the process of the invention and used multiple times in the process of the invention.

[0094] The process according to the invention is carried out in the presence of molecular hydrogen or a hydrogen source.

[0095] According to any of the above embodiments of the present invention, the hydrogen source may be a transfer hydrogenation agent. Specific and non-limiting examples of catalytic transfer hydrogenation agents are tetralin, formic acid, formate (e.g. sodium formate, potassium formate or ammonium formate), limonene or mixtures thereof. In particular, the transfer hydrogenation agent may be tetralin, formic acid, formate, limonene or mixtures thereof. Even more particularly, the transfer hydrogenation agent may be formic acid, formate, limonene or mixtures thereof.

[0096] The transfer hydrogen agent can be added to the reaction medium of the inventive method in a wide range of concentrations. As non-limiting examples, the hydrogen source concentration values ​​ranging from 0.01mol% to 100mol%, even 0.01mol% to 10mol%, and even 0.01mol% to 5mol% can be cited relative to the amount of the substrate. When only a small portion produces molecular hydrogen, a large amount of transfer hydrogenating agents are used. For example, about 10% of tetralin is converted into molecular hydrogen. It goes without saying that, as known to those skilled in the art, the optimum concentration of the hydrogen source will depend on the properties of the latter, the properties of the substrate, the temperature and the catalyst used in the process of the method, and the time required for the reaction.

[0097] According to any of the above embodiments of the present invention, as an alternative to the transfer hydrogenation agent, molecular hydrogen can be used in a pure state or mixed with an inert gas. Specific and non-limiting examples of such inert gases are nitrogen or argon. 2 The volume ratio of the inert gas to the inert gas is 1 / 1 to 0.01 / 1, and more preferably the ratio is 0.05 / 1.

[0098] Molecular hydrogen can be added to the reaction medium of the inventive method with a wide range of concentrations. As non-limiting examples, the molecular hydrogen concentration value of 0.01mol% to 100mol% can be cited relative to the amount of substrate. Preferably, the hydrogen source concentration is 0.01mol% to 10mol% relative to the amount of substrate. Preferably, the hydrogen source concentration is 0.01mol% to 8mol% relative to the amount of substrate. Even more preferably, the hydrogen source concentration is 0.01mol% to 5mol% relative to the amount of substrate. Of course, those skilled in the art can regulate the pressure or flow (such as in a continuous process) of molecular hydrogen to obtain the concentration range according to whether the method is intermittent or continuous. Those skilled in the art can also regulate the concentration of molecular hydrogen according to the dilution of substrate in catalyst loading and solvent.

[0099] In the method of the present invention, the hydrogen source or molecular hydrogen is present in an amount of 0.01 mol% to 10 mol%, even 0.01 mol% to 8 mol%, more even 0.01 mol% to 5 mol%, relative to the amount of the substrate.

[0100] The process of the present invention can be carried out in a batch or continuous manner. According to a particular embodiment of the present invention, the process is carried out in a continuous manner, since this allows a higher productivity to be obtained.

[0101] The reaction can be carried out in the presence or absence of a solvent. When a solvent is required or used for practical reasons, any solvent of the type of reaction at the time may be used for the purposes of the present invention. Non-limiting examples include C 6-12Aromatic solvents such as toluene, 1,3-diisopropylbenzene, p-cymene, cumene, pseudocumene, benzyl acetate, xylene or mixtures thereof, C 3-16 Alkanes such as hexadecane, ether solvents such as tetrahydrofuran, butyl ether, methyltetrahydrofuran or mixtures thereof. In particular, the boiling point of the solvent is above 100° C. The choice of solvent depends on the nature of the substrate and the complex, and a person skilled in the art is fully capable of selecting the most convenient solvent in each case to optimize the reaction.

[0102] The isomerization can be carried out at a temperature of 120° C. to 300° C. For a continuous process, it is more preferably 150° C. to 250° C., and for a batch process, it is more preferably 150° C. to 200° C. Of course, those skilled in the art will also be able to select the preferred temperature based on the melting and boiling points of the starting and final products and the time required for the reaction or conversion.

[0103] According to any of the above embodiments of the present invention, the compound of formula (II) can be prepared according to a variety of methods known in the art, such as Diels-Alder reaction, cyclization reaction or Friedel-Crafts reaction. Those skilled in the art will be able to select the best conditions to prepare the compound of formula (II). In particular, the method of the present invention also includes preparing the compound of formula (IIa) from the following compound:

[0104]

[0105] The compound is in the form of any stereoisomer or a mixture thereof; wherein n, R 1 and R 2 has the same meaning as defined above, and m' is an integer from 0 to 7. The preparation of the compound of formula (IIa) from the compound of formula (XI) can be carried out under normal conditions known to those skilled in the art, i.e. in the presence of an acid such as a Bronsted acid or a Lewis acid. The preparation of the compound of formula (IIa) from the compound of formula (XI) can include the step of treating the compound of formula (XI) with an acid. According to a specific embodiment of the present invention, the acid used to prepare the compound of formula (IIa) may have a pKa lower than 3. Specific and non-limiting examples of Bronsted acids can be selected from the group consisting of phosphoric acid, p-toluenesulfonic acid, methanesulfonic acid, camphorsulfonic acid, methanedisulfonic acid, methanetrisulfonic acid, 2,4-dinitrobenzenesulfonic acid. In particular, the Bronsted acid can be phosphoric acid. Specific and non-limiting examples of Lewis acids can be selected from the group consisting of: metal trifluoromethanesulfonates, such as Al(OTf) 3 , lanthanide triflates, such as Sc(OTf) 3 、Bi(OTf) 3 , metal tetrafluoroborate, such as Zn(BF4 ) 2 , and metal halides such as AlX 3 ,RAlX 2 , R 2 AlX、BX 3 (where X is a halide, R is C 1-3 Alkyl), ZnCl 2 , ZnBR 2 .

[0106] According to any embodiment of the present invention, m' may be an integer from 0 to 5. In particular, m' may be an integer from 0 to 3. In particular, m' may be an integer from 0 to 2. Even more particularly, m' may be 1.

[0107] According to any of the above embodiments of the present invention, the compound of formula (XI) conforms to the following formula:

[0108]

[0109] The compound is in the form of any stereoisomer or a mixture thereof; wherein n, R 1 , R 6 , R 8 and R 9 has the same meaning as defined above.

[0110] Non-limiting examples of suitable compounds of formula (XII) may include 3,7-dimethyloct-6-ene-1-yn-3-ol, 3,6,7-trimethyloct-6-ene-1-yn-3-ol. The compound of formula (IIa) starting from 3,6,7-trimethyloct-6-ene-1-yn-3-ol is 1-(3-isopropyl-3-methylcyclopent-1-ene-1-yl)ethan-1-one, 1-(3,3,4-trimethylcyclohex-1-ene-1-yl)ethan-1-one or a mixture thereof.

[0111] Acid can be added to the reaction medium of the inventive method with a wide range of concentrations. As non-limiting examples, an acid concentration value in the range of 0.01 to 10 equivalents relative to the amount of substrate can be cited, preferably in the range of 0.1 to 2 equivalents relative to the amount of substrate. As known to those skilled in the art, the optimum concentration of acid depends on the properties of the latter, the properties of the substrate and the temperature used in the process of the method and the time required for the reaction.

[0112] The reaction can be carried out in the presence or absence of a solvent. When a solvent is required or used for practical reasons, any solvent of the type of reaction at the time may be used for the purposes of the present invention. Non-limiting examples include C 6-12Aromatic solvents such as toluene, 1,3-diisopropylbenzene, cumene, pseudocumene, benzyl acetate, xylene or mixtures thereof, C 3-16 Alkanes such as hexadecane, hexane, heptane, cyclohexane, ether solvents such as tetrahydrofuran, methyltetrahydrofuran or mixtures thereof. The choice of solvent depends on the nature of the substrate and the nature of the acid, and the skilled person is fully capable of selecting the most convenient solvent in each case to optimize the reaction.

[0113] The temperature for preparing the compound of formula (IIa) from the compound of formula (XI) is 50° C. to 180° C. More preferably, it is 70° C. to 120° C. Of course, those skilled in the art can also select the preferred temperature based on the melting point and boiling point of the starting and final products and the time required for the reaction or conversion.

[0114] According to any embodiment of the present invention, the compound of formula (I) 1-(5,5-dimethylcyclohexene-1-yl) ethyl-1-one can be further converted into 1-(5,5-dimethyl-1-cyclohexene-1-yl)-4-pentene-1-one. The preparation of 1-(5,5-dimethyl-1-cyclohexene-1-yl)-4-pentene-1-one from 1-(5,5-dimethylcyclohexene-1-yl) ethyl-1-one is well known in the art, for example under allylation conditions. Those skilled in the art will be able to select optimal conditions to prepare 1-(5,5-dimethyl-1-cyclohexene-1-yl)-4-pentene-1-one. Therefore, another object of the present invention is a method for preparing 1-(5,5-dimethyl-1-cyclohexene-1-yl)-4-pentene-1-one, comprising the following steps:

[0115] a) isomerizing 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one by contacting it with a catalyst system comprising:

[0116] i) palladium (Pd); and

[0117] ii) molecular hydrogen or a source of hydrogen,

[0118] To obtain 1-(5,5-dimethylcyclohex-1-en-1-yl)ethan-1-one;

[0119] b) Converting 1-(5,5-dimethylcyclohex-1-en-1-yl)ethan-1-one into 1-(5,5-dimethyl-1-cyclohexen-1-yl)-4-penten-1-one.

[0120] Typical ways of carrying out the process of the invention are reported in the examples hereinafter. DETAILED DESCRIPTION

[0121] Example

[0122] The present invention will now be described in further detail by the following examples, wherein abbreviations have the usual meanings in the art, temperatures are expressed in degrees Celsius (°C); 1 H) and 100MHz( 13 C) or a Bruker Avance II Ultrashield 400plus operating at 500 MHz ( 1 H) and 125MHz( 13 C) or a Bruker Avance III 500 operating at 600 MHz ( 1 H) and 150MHz( 13 NMR spectra were obtained using a Bruker Avance III 600 cryoprobe operated at 40 °C. Spectra were internally referenced to 0.0 ppm tetramethylsilane. 1 H NMR signal shifts are expressed in δ ppm and coupling constants (J) are expressed in Hz with the following multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; b, broad peak (indicating unresolved coupling) and were interpreted using Bruker Topspin software. 13 C NMR data are presented as chemical shifts δ ppm and hybridization from DEPT90 and DEPT 135 experiments, C, quaternary (s); CH, methine (d); CH 2 , methylene(t); CH 3 , methyl (q).

[0123] Example 1

[0124] Preparation of 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one

[0125] 500 g (0.6 eq.) of 85% phosphoric acid and 4,400 g of heptane were charged into the reactor. The mixture was stirred and heated to reflux by a Dean-Stark apparatus. 1100 g (1 eq.) of 3,7-dimethyloct-6-ene-1-yn-3-ol was added over 6 hours and then refluxed for 4 hours. The reaction mixture was cooled to 60°C and water was added. The acid phase was discharged and the organic phase was washed with 60°C water. The solvent was concentrated under vacuum. 1050 g of crude material was obtained, and after fractionation (Bp 80°C / 10.9 mbar), 605 g of 1-(3,3-dimethylcyclohex-1-ene-1-yl) ethyl-1-one with a purity of 95% was obtained.

[0126] 1 H-NMR (500MHz, CDCl 3), δ (ppm): 6.53 (t, 1H); 2.27 (s, 3H); 2.15 (td, 2H); 1.61 (m, 2H); 1.43 (m, 2H); 1.06 (s, 6H)

[0127] 13 C-NMR (125MHz, CDCl 3 ), δ (ppm): 199.9; 149.7; 137.3; 36.3; 32.7; 29.1; 25.2; 23.1; 19.1.

[0128] Example 2

[0129] Preparation of 1-(3-ethyl-3-methyl-cyclohexen-1-yl)ethan-1-one

[0130] According to the procedure in Example 1, 3,7-dimethylnon-6-en-1-yn-3-ol (310.0 g) was converted to 1-(3-ethyl-3-methyl-cyclohexen-1-yl)ethan-1-one (170.5 g, purity 94%) after fractional distillation (Bp 98° C. / 12.0 mbar).

[0131] 1 H-NMR (500MHz, CDCl 3 ), δ (ppm): 6.55 (t, 1H); 2.28 (s, 3H); 2.12-2.05 (m, 1H); 1.69-1.63 (m, 1H); 1.52-1.33 (m, 4H); 1.02 (s, 3H); 0.87 (t, 3H)

[0132] 13 C-NMR (125MHz, CDCl 3 ), δ (ppm): 199.8; 149.3; 138.0; 35.7; 34.5; 33.2; 26.1; 25.3; 23.3; 18.9; 8.4.

[0133] Example 3

[0134] Preparation of 1-(3-isopropyl-3-methyl-cyclopenten-1-yl)ethan-1-one

[0135] According to the procedure in Example 1, 3,6,7-trimethyloct-6-ene-1-yn-3-ol (310.0 g) was converted into 1-(3-isopropyl-3-methyl-cyclopenten-1-yl)ethan-1-one (165.8 g, purity 96%) after fractional distillation (Bp 96° C. / 12.0 mbar).

[0136] 1 H-NMR (500MHz, CDCl 3), δ (ppm): 6.52 (t, 1H); 2.55-2.51 (m, 2H); 2.31 (s, 3H); 1.89-1.83 (m, 1H); 1.71-1.65(m,1H); 1.59-1.53(m,1H); 1.04(s,3H); 0.91(d,3H); 0.87(d,3H)

[0137] 13 C-NMR (125MHz, CDCl 3 ), δ (ppm): 197.5; 152.2; 143.2; 53.5; 35.9; 33.5; 29.6; 26.7; 22.5; 18.4; 18.0.

[0138] Example 4

[0139] Preparation of 1-(3,3-dimethylcyclohexa-1,4-dien-1-yl)ethan-1-one

[0140] Place 20.3 g of Δ 3 -carene, 150 mL of methanol and 150 mL of dichloromethane. The resulting solution was cooled to -78 °C and then washed with O 3 Treat for 2 hours. Triphenylphosphine (40.9 g) in dichloromethane (50 mL) was slowly added over 30 minutes at -35°C to -25°C, and the reaction mixture was stirred for 45 minutes, then the volatiles were concentrated and flash evaporated to give 14.5 g of 95% pure 2-(3-acetonyl-2,2-dimethyl-cyclopropyl)acetaldehyde, which was used without further purification.

[0141] Next, 2-(3-acetonyl-2,2-dimethyl-cyclopropyl)acetaldehyde (20.0 g) was poured into an ice-cold solution of NaOH (18.3 g) in water (170 mL) and EtOH (100 mL). After standing at room temperature for 16 h, H 2 O (250 mL), the mixture was extracted with ethyl acetate (2×100 mL). The combined extracts were then washed with 10% citric acid until pH = 5, and then with 10% KHCO 3 Wash until pH = 8, and finally use H 2 The solvent was removed from the combined organic phases under reduced pressure and then fractionated (Bp 94° C. / 11.0 mbar) to obtain 14.8 g of 1-(3,3-dimethylcyclohexa-1,4-dien-1-yl)ethan-1-one with a purity of 98%.

[0142] 1 H-NMR (500MHz, CDCl 3), δ (ppm): 6.62 (q, 1H); 5.69 (dt, 1H); 5.52 (dq, 1H); 2.80 (m, 2H); 2.33 (s, 3H); 1.14 (s, 6H)

[0143] 13 C-NMR (125MHz, CDCl 3 ), δ (ppm): 199.3; 147.2; 133.2; 121.6; 34.5; 29.9; 27.6; 25.1; 24.4.

[0144] Example 5

[0145] Catalytic Isomerization of 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one using Pd / C

[0146] Scheme 1: 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one (1430 g, 95%), 28 g of 5% Pd / C (50% water) and 250 g of p-cymene were stirred at 175°C, and then 22.8 g (8% mol) of formic acid was slowly added over 20 hours. The reaction mixture was cooled to 20°C, filtered, and then fractionated to obtain three fractions, namely 1-(3,3-dimethylcyclohexyl)ethan-1-one (114 g, Bp 63°C / 10 mbar), 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one (429 g, Bp 78°C / 10 mbar) and 1-(5,5-dimethylcyclohex-1-en-1-yl)ethan-1-one (858 g, Bp 83°C / 10 mbar).

[0147] Scheme 2: 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one (200 g, 95%) and 4 g of 5% Pd / C (50% water) were stirred at 175°C, and then a 2% hydrogen solution in nitrogen (equivalent to 8% mol hydrogen) was passed into the suspension for 20 hours. The reaction mixture was cooled to 20°C, filtered, and then fractionated to obtain 3 fractions, namely 1-(3,3-dimethylcyclohexyl)ethan-1-one (14 g, Bp 63°C / 10 mbar), 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one (60 g, Bp 78°C / 10 mbar) and 1-(5,5-dimethylcyclohex-1-en-1-yl)ethan-1-one (120 g, Bp 83°C / 10 mbar).

[0148] 1 H-NMR (700MHz, CDCl 3), δ (ppm): 6.87 (m, 1H); 2.28 (m, 2H); 2.28 (s, 3H); 2.01 (q, 2H); 1.34 (t, 2H); 0.9 (s, 6H)

[0149] 13 C-NMR (175MHz, CDCl 3 ), δ (ppm): 199.5; 139.7; 138.7; 36.4; 34.2; 28.5; 28.0; 25.3; 24.1.

[0150] Example 6

[0151] Catalytic Isomerization of 1-(3-ethyl-3-methyl-cyclohexen-1-yl)ethan-1-one using Pd / C

[0152] The catalytic isomerization of 1-(3-ethyl-3-methyl-cyclohexen-1-yl)ethan-1-one was carried out according to Scheme 1 described in Example 5. The final composition was determined by GC-MS and NMR analysis with a conversion of 69%. The crude reaction mixture was purified by column chromatography to give 49% of 1-(5-ethyl-5-methyl-cyclohexen-1-yl)ethan-1-one. No other regioisomers were detected.

[0153] 1 H-NMR (500MHz, CDCl 3 ), δ (ppm): 6.89 (m, 1H); 2.29 (s, 3H); 2.28-2.25 (m, 2H); 2.01 (td, 2H); 1.37-1.35 (m, 2H); 1.29-1.24 (m, 2H); 0.85 (t, 3H); 0.83 (s, 3H)

[0154] 13 C-NMR (125MHz, CDCl 3 ), δ (ppm): 199.6; 140.1; 138.6; 34.8; 33.5; 31.9; 31.1; 25.4; 23.9; 23.7; 7.8.

[0155] Example 7

[0156] Catalytic Isomerization of 1-(3,3-dimethylcyclohexa-1,4-dien-1-yl)ethan-1-one Using Pd / C

[0157] 1-(3,3-Dimethylcyclohexa-1,4-dien-1-yl)ethan-1-one was isomerized according to Scheme 2 described in Example 5. 1-(5,5-dimethylcyclohexa-1,3-dien-1-yl)ethan-1-one was formed with a conversion of 55% and a yield of 15%, as determined by GC-MS and NMR analysis.

[0158] 1 H-NMR (500MHz, CDCl 3 ), δ (ppm): 6.88 (d, 1H); 6.01-5.95 (m, 2H); 2.36 (s, 2H); 2.33 (s, 3H); 1.01 (s, 6H)

[0159] 13 C-NMR (125MHz, CDCl 3 ), δ (ppm): 199.2; 153.2; 136.1; 132.7; 117.5; 41.2; 34.0; 27.7; 27.1.

[0160] Example 8

[0161] Catalytic Isomerization of 1-(3-isopropyl-3-methyl-cyclopenten-1-yl)ethan-1-one using Pd / C

[0162] 1-(3-Isopropyl-3-methyl-cyclopenten-1-yl)ethan-1-one was isomerized according to Scheme 2 described in Example 5. 1-(4-isopropyl-4-methyl-cyclopenten-1-yl)ethan-1-one was formed with a conversion of 63% as determined by GC-MS and NMR analysis, and no other regioisomers were detected.

[0163] Example 9

[0164] Catalytic Isomerization of 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one using Pd / C in EtOH (Comparative Example)

[0165] The isomerization of 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one was carried out under the same reaction conditions as described by Takasago (EP1162190A2), using Pd / C instead of RhCl 3 ·3H 2 O catalyst. No isomerization occurred after 23 hours.

Claims

1. A method for preparing a 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivative comprising isomerizing an intracyclic carbon-carbon double bond, wherein the isomerization is carried out by contacting a substrate containing conjugated intracyclic carbon-carbon double bonds with a catalyst system comprising: i) palladium (Pd); and ii) Molecular hydrogen or a source of hydrogen.

2. The method according to claim 1, wherein the 1-(cycloalkane-1-en-1-yl)acyl or 1-(cycloalkadien-1-yl)acyl derivative is a compound of the formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein one dotted line is a carbon-carbon single bond and the other is a carbon-carbon single bond or a carbon-carbon double bond; m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

3. The method according to any one of claims 1 to 2, wherein the substrate is a compound of the formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein one dotted line is a carbon-carbon single bond and the other is a carbon-carbon single bond or a carbon-carbon double bond; m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

4. The method according to any one of claims 1 to 3, wherein the compound of formula (I) conforms to the following formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and The substrate is a compound of the formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein m is an integer from 0 to 7; n is an integer from 1 to 8; R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 alkoxy; and each R 2 Simultaneously or independently represent a substituent on the ring, which is C 1-6 Alkyl or C 2-6 Alkenyl; or two R 2 Group or R 1 With an R 2 The groups combine to form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy.

5. The method according to any one of claims 1 to 4, wherein m is an integer from 0 to 2, preferably m is 1.

6. The method according to any one of claims 1 to 5, wherein each R 2 Simultaneously or independently C 1-3 Alkyl; or two R 2 The groups combine to form C 5-6 Cycloalkyl, preferably R 2 It is methyl.

7. The method according to any one of claims 1 to 6, wherein the compound of formula (I) is a compound of the following formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; each R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 Each independently represents a hydrogen atom, C 1-6 Alkyl or C 2-6 alkenyl; or R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 The two groups in the 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; or R 3 With R 1 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; or R 4 With R 1 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; provided that R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 Such that the compound of formula (V) is different from the compound of formula (VI) as defined below; And the compound of formula (II) conforms to the following formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 has the same meaning as defined above.

8. The method according to claim 7, wherein the compound of formula (V) is a compound of the following formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; each R 8 and R 9 Each independently represents a hydrogen atom, C 1-6 Alkyl or C 2-6 alkenyl; or R 8 and R 9 Together they form C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, each of which is optionally substituted with one or more C 1-6 Alkyl, C 2-6 Alkenyl or C 1-6 Alkoxy; And the compound of formula (VI) conforms to the following formula: The compound is in the form of any stereoisomer or a mixture thereof, wherein R 1 , R 8 and R 9 has the same meaning as defined above.

9. The method according to any one of claims 1 to 8, wherein R 1 C 1-3 Alkyl, n is 2.

10. The process according to any one of claims 1 to 9, wherein the palladium is supported on carbon.

11. The method according to any one of claims 1 to 10, wherein the hydrogen source is tetralin, formic acid, formate, limonene or a mixture thereof.

12. The process according to any one of claims 1 to 11, wherein the process is a continuous process.

13. The method according to any one of claims 1 to 12, wherein the method further comprises preparing a compound of formula (IIa) from a compound of the following formula: The compound is in the form of any stereoisomer or a mixture thereof; wherein, n、R 1 and R 2 has the same meaning as defined in claims 1 to 11, and m' is an integer from 0 to 7.

14. The process according to claim 13, wherein preparing the compound of formula (IIa) from the compound of formula (XI) comprises the step of treating the compound of formula (XI) with an acid.

15. A method for preparing 1-(5,5-dimethyl-1-cyclohexene-1-yl)-4-penten-1-one, comprising the following steps: a) isomerizing 1-(3,3-dimethylcyclohex-1-en-1-yl)ethan-1-one by contacting it with a catalyst system comprising: i) palladium (Pd); and ii) molecular hydrogen or a source of hydrogen, To obtain 1-(5,5-dimethylcyclohex-1-en-1-yl)ethan-1-one; b) Converting 1-(5,5-dimethylcyclohex-1-en-1-yl)ethan-1-one into 1-(5,5-dimethyl-1-cyclohexen-1-yl)-4-penten-1-one.

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