Hydrogenation method of unsaturated esters

Abstract

The present invention relates to a method for hydrogenating an ester-containing substrate. More particularly, the present invention relates to a method for reducing an α,β-γ,δ unsaturation-containing ester of formula (I) and a β,γ unsaturation-containing ester to produce an alcohol of formula (II). The method of the present invention uses a base, the conjugate acid of which has a pKa of 4 to 15. The method of the present invention finds use in the synthesis of organic molecules.

Description

[Technical Field]

[0001] Technical field to which the invention belongs The present invention relates to a method for hydrogenating ester-containing substrates. More specifically, the present invention relates to a method for reducing α,β-γ,δ unsaturated esters and β,γ unsaturated esters.

[0002] Background of the Invention Ester reduction is an essential conversion in the chemical industry as a pathway to primary alcohols. Traditionally, ester reduction has been carried out using reagents such as sodium metal in ethanol (in stoichiometric or excess amounts) (Bouveault-Blanc reduction), or more recently, metal hydride reagents such as LiAlH4 and NaBH4. However, these reduction reactions are difficult to carry out on a large scale and effectively, particularly due to safety concerns associated with the extremely exothermic quenching process. Thus, research on ester reduction has more recently focused on catalytic reduction using hydrogen gas. For example, Cu or Zn-based heterogeneous catalysts are used very extensively for ester reduction, mainly in the natural detergent alcohol (NDA) market. However, these methods require very high pressure and / or temperature, in addition to large-scale, dedicated manufacturing facilities. Furthermore, the chemoselectivity of ester reduction, compared to other highly sensitive functional groups, can be a problem when using these methods.

[0003] The reduction of unsaturated esters, such as α,β-γ,δ unsaturated esters and β,γ unsaturated esters, can be particularly problematic. Finding conditions for chemoselective reduction of the ester group while maintaining the regiochemistry of the alkenyl functional group is especially difficult.

[0004] For ease of understanding, α, β, γ, and δ, when used in the context of unsaturated esters, refer to carbon atoms in the ester-containing substrate. α, β, γ, and δ are used to indicate carbon atoms in which an alkene (C=C) or alkyne (C≡C) bond exists. Scheme 1 below shows the positions of α, β, γ, and δ carbons in a typical ester-containing substrate, and this notation rule will be used herein and throughout. Thus, for example, a β,γ-unsaturated ester contains an alkene bond between the β and γ carbons, while an α,β-γ,δ unsaturated ester contains two alkene bonds (i.e., an alkene bond between the α and β carbons, and an alkene bond between the γ and δ carbons). [ka]

[0005] Many methods for esterification hydrogenation using transition metal catalysts have been developed, but these methods often result in reduction of the alkenyl functional group or a regiochemical change of the alkenyl functional group.

[0006] Therefore, there is still a need for a method that can selectively reduce unsaturated esters, particularly α,β-γ,δ unsaturated esters and β,γ unsaturated esters, while maintaining the regiochemistry of alkenyl functional groups. [Overview of the Initiative]

[0007] Therefore, the present invention provides a method for hydrogenating α,β-γ,δ unsaturated esters or β,γ unsaturated esters. This method has high chemoselectivity for hydrogenating the ester group of α,β-γ,δ unsaturated esters and β,γ unsaturated esters to the corresponding alcohol while maintaining the regiochemistry and / or stereochemistry of the alkenyl and / or alkynyl functional group.

[0008] In a first aspect of the present invention, a method is provided for producing an alcohol of formula (II) by hydrogenating an ester-containing substrate of formula (I), [ka] The above method includes treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen. The ester-containing substrate of formula (I) includes α,β-γ,δ unsaturated esters or β,γ unsaturated esters; R u This is an organic group having 3 to 70 carbon atoms, however, R u The carbonyl carbon of the ester portion ( * Conditional on the bond forming an α,β-γ,δ unsaturated ester or β,γ unsaturated ester of formula (I); R v A is an organic group having 1 to 70 carbon atoms; The conjugate acid of a base has a pKa of 4 to 15.

[0009] A remarkable advantage of the present invention is that the hydrogenation of α,β-γ,δ unsaturated esters or β,γ unsaturated esters is R u The reaction proceeds without reducing the alkenyl functional group of the group, and between the ester-containing substrate of formula (I) and the alcohol of formula (II), R u The regiochemistry and / or stereochemistry of the group are maintained. In other words, R uThe group is the same in the ester-containing substrate of formula (I) and the alcohol of formula (II). The conjugate acid of the base of the present invention has a pKa of 4 to 15 and can be considered a weak base. While we do not wish to be bound by any theory, it is thought that in the hydrogenation method of the present invention, by using a base with a conjugate acid pKa of 4 to 15, the conjugation of the carbonyl group and the alkenyl functional group is prevented, and the formation of enolate intermediates is minimized or prevented. It is speculated that the formation of such enolate intermediates may result in the reduction of the alkenyl functional group and the loss of the regiochemistry of the alkene. Furthermore, it is thought that the formation of enolate intermediates may lead to the formation of other undesirable byproducts, such as those resulting from cycloaddition reactions (e.g., Diels-Alder) or condensation reactions. It is even more surprising that in the hydrogenation method of the present invention, by using a base with a conjugate acid pKa of 4 to 15, the activity of the transition metal catalyst is activated and maintained.

[0010] The reduction of cinnamic acid esters containing α,β unsaturated esters using transition metal catalysts has been reported (e.g., de Vries et al., Adv. Synth. Catal. 2018, 360). However, conditions that may be suitable for hydrogenating cinnamic acid esters may not be suitable for the ester-containing substrate of formula (I). In other words, the inventors do not believe that cinnamic acid esters form an enolate intermediate during the hydrogenation process carried out under basic conditions, and therefore, as mentioned above, they do not suffer from the same problems as the ester-containing substrate of formula (I). [Brief explanation of the drawing]

[0011] [Figure 1] Figure 1 shows an exemplary reaction scheme for the conversion of the ester-containing substrate of formula (I) to the corresponding alcohol of formula (II).

[0012] definition The bonding points of a partial or substituent are represented by "-". For example, -OH is bonded via an oxygen atom.

[0013] Unless expressly otherwise stated, the structures shown herein include all conformational or geometric isomers of such structures. For example, where an alkene double bond is shown, both E and Z (or cis and trans) isomers are intended and included, and where two or more alkene double bonds are shown, all conformational or geometric isomers are included and intended (e.g., E,E; E,Z; Z,E; and Z,Z; as well as cis, cis; cis, trans; trans, cis; and trans, trans).

[0014] As used herein, the terms “maintenance of regiochemistry” and “retention of regiochemistry” refer to the maintenance or retention of the position of any given functional group, such as a β,γ alkene bond.

[0015] As used herein, the term “geometry” is used to refer to the geometric or conformational structure of a molecule or functional group, for example, the conformation of an E or Z (or cis or trans) alkene bond.

[0016] As used herein, the term "alkyl" may include linear or branched saturated hydrocarbon groups. In certain embodiments, alkyl groups may have 1 to 20 carbon atoms, in certain embodiments 1 to 15 carbon atoms, and in certain embodiments 1 to 8 carbon atoms. Alkyl groups may be unsubstituted or substituted. Unless otherwise specified, alkyl groups may be bonded to any suitable carbon atom, and if substituted, may be substituted to any suitable atom. Typical alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, and n-hexyl.

[0017] As used herein, the term "alkenyl" refers to a linear or branched unsaturated hydrocarbon group containing at least one carbon-carbon double bond.

[0018] As used herein, the term "alkynyl" refers to a linear or branched unsaturated hydrocarbon group containing at least one carbon-carbon triple bond.

[0019] As used herein, the term "cycloalkyl" is used to refer to a saturated carbocyclic hydrocarbon group. Cycloalkyl groups may have a monocyclic or multiple fused rings. In certain embodiments, cycloalkyl groups may have 3 to 15 carbon atoms, in certain embodiments 3 to 10 carbon atoms, and in certain embodiments 3 to 8 carbon atoms. Cycloalkyl groups may be unsubstituted, or they may be substituted. Unless otherwise specified, cycloalkyl groups may be bonded with any suitable carbon atom, and if substituted, they may be substituted with any suitable atom. Typical cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and adamantyl.

[0020] As used herein, the term "cycloalkenyl" refers to an unsaturated, non-aromatic carbon ring. Therefore, a cycloalkenyl group has at least one carbon-carbon double bond, but may have more. In certain embodiments, a cycloalkenyl group may have 3 to 15 carbon atoms, in certain embodiments 3 to 10 carbon atoms, and in certain embodiments 3 to 8 carbon atoms. A cycloalkenyl group may be unsubstituted, or it may be substituted. Unless otherwise specified, a cycloalkenyl group may be bonded to any suitable carbon atom, and if substituted, it may be substituted to any suitable atom. Typical cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, and cyclohexenyl.

[0021] As used herein, the term "alkoxy" refers to an optionally substituted group of the formula alkyl-O or cycloalkyl-O- (wherein alkyl and cycloalkyl are as defined above).

[0022] As used herein, the term "aryl" refers to an aromatic carbocyclic group. An aryl group may have a monocyclic or fused ring. In certain embodiments, an aryl group may have 6 to 20 carbon atoms, in certain embodiments 6 to 15 carbon atoms, and in certain embodiments 6 to 12 carbon atoms. An aryl group may be unsubstituted, or it may be substituted. Unless otherwise specified, an aryl group may be bonded to any suitable carbon atom, and if substituted, it may be substituted to any suitable atom. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, and anthracenyl.

[0023] As used herein, the term "arylalkyl" refers to an optionally substituted group of the formula aryl-alkyl- (wherein aryl and alkyl are as defined above).

[0024] As used herein, the terms "halogen," "halo," or "hal" refer to -F, -Cl, -Br, and -I.

[0025] As used herein, the term “heteroalkyl” refers to a linear or branched saturated hydrocarbon group in which one or more carbon atoms are independently replaced by one or more heteroatoms (e.g., nitrogen, oxygen, phosphorus, and / or sulfur atoms). Heteroalkyl groups may be unsubstituted or substituted. Unless otherwise specified, heteroalkyl groups may be bonded with any suitable atom, and if substituted, may be substituted with any suitable atom. Examples of heteroalkyl groups include, but are not limited to, ethers, thioethers, primary amines, secondary amines, and tertiary amines.

[0026] As used herein, the term “heterocycloalkyl” refers to a saturated cyclic hydrocarbon group in which one or more carbon atoms are independently replaced by one or more heteroatoms (e.g., nitrogen, oxygen, phosphorus, and / or sulfur atoms). Heterocycloalkyl groups may be unsubstituted or substituted. Unless otherwise specified, heterocycloalkyl groups may be bonded with any suitable atom, and if substituted, may be substituted with any suitable atom. Examples of heterocycloalkyl groups include, but are not limited to, epoxides, morpholinyl, piperidinyl, piperazinyl, tyranyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, and thiomorpholinyl.

[0027] As used herein, the term “heteroaryl” refers to an aromatic carbocyclic group in which one or more carbon atoms are independently replaced by one or more heteroatoms (e.g., nitrogen, oxygen, phosphorus, and / or sulfur atoms). Heteroaryl groups may be unsubstituted or substituted. Unless otherwise specified, heteroaryl groups may be bonded with any suitable atom, and if substituted, may be substituted with any suitable atom. Examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, thiophenyl, oxadiazolyl, pyridinyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl.

[0028] As used herein, the term “heterocyclic” includes both heterocycloalkyl groups and heteroaryl groups.

[0029] As used herein, the term "substituted" refers to a group in which one or more hydrogen atoms are each independently replaced by a substituent (e.g., 1, 2, 3, 4, 5 or more), which may be the same or different. Examples of substituents include -halo, -C(halo)3, -R c =O, =S, -O-R c -S-R c -NR c R d -CN, -NO2, -C(O)-R c -COOR d -C(S)-R c -C(S)OR d -S(O)2OH, -S(O)2-R c -S(O)2NR c R d -O-S(O)-R c and -CONR c R d For example, -halo, -C(halo)3 (e.g., -CF3), -R c -O-R c -NR c R d -CN, or -NO2, but are not limited thereto. R c and R d are each independently selected from the group consisting of H, alkyl, aryl, arylalkyl, heteroalkyl, heteroaryl, or R c and R d together with the atom to which they are attached form a heterocycloalkyl group. R c and R d may be unsubstituted or further substituted as defined herein.

[0030] As used herein, the term “fatty acid” refers to a carboxylic acid having a long aliphatic chain (e.g., more than 6 carbon atoms), which may be either saturated or unsaturated. The aliphatic chain of a fatty acid may be branched or unbranched. In certain embodiments, the aliphatic chain of a fatty acid contains 12 to 24 carbon atoms. In certain embodiments, the aliphatic chain of a fatty acid contains 0 to 5 carbon-carbon double bonds.

[0031] As used herein, the term “aliphatic alcohol” refers to an alcohol having a long aliphatic chain (e.g., more than 6 carbon atoms) which may be either saturated or unsaturated. The aliphatic chain of a fatty alcohol may be branched or unbranched. In certain embodiments, the aliphatic chain of a fatty alcohol contains 12 to 24 carbon atoms. In certain embodiments, the aliphatic chain of a fatty alcohol contains 0 to 5 carbon-carbon double bonds.

[0032] As used herein, the term "wax ester" or "waxy ester" refers to an ester of a fatty acid and a fatty alcohol, where the fatty acid and fatty alcohol are as defined above.

[0033] As used herein, the term “bidentate ligand” refers to a ligand that donates two pairs of electrons to a metal atom.

[0034] As used herein, the term “tridentate ligand” refers to a ligand that donates three pairs of electrons to a metal atom.

[0035] As used herein, the term "tetradentate ligand" refers to a ligand that donates four pairs of electrons to a metal atom.

[0036] As used herein, the term "Ru-SNS" refers to dichlorotriphenylphosphine [bis(2-(ethylthio)ethyl)amine]ruthenium(II).

[0037] As used herein, the term "Ru-PNN" refers to dichlorotriphenylphosphine [2-(diphenylphosphino)-N-(2-pyridinylmethyl)ethaneamine]ruthenium(II).

[0038] As used herein, the term "Ru-SNN" refers to dichlorotriphenylphosphine [2-(ethylthio)-N-(2-pyridinylmethyl)ethaneamine]ruthenium(II).

[0039] As used herein, the term "S / C" is an abbreviation for "substrate / catalyst" and is used to represent the catalyst load used in a reaction, i.e., the molar ratio of ester-containing substrate to catalyst present in the reaction mixture. If the ester-containing substrate contains more than one ester moiety, the S / C value is adjusted accordingly. For example, a molar ratio of triglyceride to catalyst of 10,000:1 is equal to an S / C of 30,000:1 (because the triglyceride substrate contains three ester moieties).

[0040] As used herein, the term "turnover number" (TON) refers to the number of moles of substrate that one mole of catalyst can convert before it becomes inactive.

[0041] Where used herein, unless otherwise specified, "mol%" refers to the molar amount of a specified substance (e.g., a base) relative to the molar amount of an ester-containing substrate as a percentage. The "mol%" amount given for a particular substance (e.g., a base) is the amount of that substance used in the reaction chamber (i.e., where the hydrogenation reaction takes place).

[0042] As used herein, the term "hydrogenation" refers to hydrogenation using molecular hydrogen.

[0043] Detailed description of the invention Preferred and / or optional features of the present invention are shown herein. Any aspect of the present invention may be combined with any other aspect of the present invention unless otherwise required in the context. Any preferred and / or optional features of any aspect may be combined, and may be used alone or in combination with any aspect of the present invention unless otherwise required in the context.

[0044] The present invention provides a method for producing an alcohol of formula (II) by hydrogenating an ester-containing substrate of formula (I), [ka] The above method includes treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen. The ester-containing substrate of formula (I) includes α,β-γ,δ unsaturated esters or β,γ unsaturated esters; R u This is an organic group having 3 to 70 carbon atoms, however, R u The carbonyl carbon of the ester portion ( * Conditional on the bond forming an α,β-γ,δ unsaturated ester or β,γ unsaturated ester of formula (I); R v A is an organic group having 1 to 70 carbon atoms; The conjugate acid of a base has a pKa of 4 to 15.

[0045] Ester-containing substrates The method of the present invention comprises hydrogenation of an ester-containing substrate of formula (I), wherein the ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester. The ester-containing substrate of formula (I) comprises at least one ester moiety.

[0046] In the preferred method of the present invention, the ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester. In the preferred method of the present invention, the ester-containing substrate of formula (I) comprises a β,γ unsaturated ester.

[0047] In the preferred method of the present invention, the ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester, wherein the bonds between the α carbon atom and the β carbon atom and the bonds between the γ carbon atom and the δ carbon atom in the α,β-γ,δ unsaturated ester, or the bonds between the β carbon atom and the γ carbon atom in the β,γ unsaturated ester, are each alkenyl bonds. When the ester-containing substrate of formula (I) is an α,β-γ,δ unsaturated ester, it is preferable that the α,β-γ,δ unsaturated ester has a cis-cis configuration, a cis-trans configuration, a trans-cis configuration, or a trans-trans configuration. When the ester-containing substrate of formula (I) is a β,γ unsaturated ester, it is preferable that the β,γ unsaturated ester has a cis configuration or a trans configuration.

[0048] The ester-containing substrate is given by formula (I): [ka] (In the formula, R u This is an organic group having 3 to 70 carbon atoms, however, R u The carbonyl carbon of the ester portion ( * Conditional on the bond forming an α,β-δ,γ unsaturated ester or β,δ unsaturated ester of formula (I); R v (This refers to an organic group having 1 to 70 carbon atoms.)

[0049] To make it understandable, R u The carbonyl carbon of the ester portion of the ester-containing substrate of formula (I) * It binds to ) to form an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester.

[0050] In the preferred method of the present invention, R u is, sp 2 It does not contain terminal CH2 groups having hybridized carbon atoms. Therefore, in the preferred method of the present invention, R u However, the carbonyl carbon of the ester portion ( *) binds to form the α,β-δ,γ unsaturated ester or β,δ unsaturated ester of formula (I), R u However, sp 2 One condition is that it does not contain terminal CH2 groups with hybridized carbon atoms.

[0051] Preferably, R u Equation (XII): [ka] (In the formula, the dashed line represents the bond of the carbonyl carbon of the ester portion of the ester-containing substrate in formula (I)) * It is an organic group that has a bond to ).

[0052] R u If is an organic group having formula (XII), then the ester-containing substrate of formula (I) includes α,β-γ,δ unsaturated esters.

[0053] R5 to R8 are each independently organic groups having either a hydrogen atom or 1 to 70 carbon atoms.

[0054] In the preferred method of the present invention, R5 to R8 are each independently a hydrogen atom, a substituted or unsubstituted carbon atom. 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl, substituted or unsubstituted C 2~70 -Alkynyl, substituted or unsubstituted C 1~70 - Heteroalkyl, substituted or unsubstituted C 3~70 -Cycloalkyl, substituted or unsubstituted C 3~70 -Cycloalkenyl, substituted or unsubstituted C 2~70 - Heterocycloalkyl, substituted or unsubstituted C 6~70 - Aryl and substituted or unsubstituted C 4~70 - Selected from heteroaryls, preferably substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 - Alkenyl, substituted or unsubstituted C 2~50 -Alkynyl, substituted or unsubstituted C 1~50 - Heteroalkyl, substituted or unsubstituted C 3~50-Cycloalkyl, substituted or unsubstituted C 3~50 -Cycloalkenyl, substituted or unsubstituted C 2~50 -Heterocycloalkyl, substituted or unsubstituted C 6~50 -Aryl, and substituted or unsubstituted C 4~50 -Heteroaryl, more preferably, substituted or unsubstituted C 1~30 -Alkyl, substituted or unsubstituted C 2~30 -Alkenyl, substituted or unsubstituted C 2~30 -Alkynyl, substituted or unsubstituted C 1~30 -Heteroalkyl, substituted or unsubstituted C 3~30 -Cycloalkyl, substituted or unsubstituted C 3~30 -Cycloalkenyl, substituted or unsubstituted C 2~30 -Heterocycloalkyl, substituted or unsubstituted C 6~30 ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​1~70 - alkyl, substituted or unsubstituted C 2~70 - alkenyl, substituted or unsubstituted C 1~70 - heteroalkyl, substituted or unsubstituted C 6~70 - aryl, and substituted or unsubstituted C 4~70 - heteroaryl, more preferably selected from substituted or unsubstituted C 1~50 - alkyl, substituted or unsubstituted C 2~50 - alkenyl, substituted or unsubstituted C 1~50 - heteroalkyl, substituted or unsubstituted C 6~50 - aryl, and substituted or unsubstituted C 4~50 - heteroaryl, even more preferably selected from substituted or unsubstituted C 1~30 - alkyl, substituted or unsubstituted C 2~30 - alkenyl, substituted or unsubstituted C 1~30 - heteroalkyl, substituted or unsubstituted C 6~30 - aryl, and substituted or unsubstituted C 4~30 - heteroaryl, even more preferably substituted or unsubstituted C 1~20 - alkyl (e.g., C 8~20 - alkyl), substituted or unsubstituted C 2~20 - alkenyl (e.g., C 8~20 - alkenyl), substituted or unsubstituted C 1~20 - heteroalkyl (e.g., C 8~20 - heteroalkyl), substituted or unsubstituted C 6~20 - aryl (e.g., C 8~20 - aryl), and substituted or unsubstituted C 4~20 - heteroaryl (e.g., C 8~20 - heteroaryl). More preferably, R5 to R8 are each independently a hydrogen atom, substituted or unsubstituted C 1~70 - alkyl, substituted or unsubstituted C 2~70 - alkenyl, and substituted or unsubstituted C 6~70 - aryl, more preferably a hydrogen atom, substituted or unsubstituted C 1~50 - alkyl, substituted or unsubstituted C 2~50 - alkenyl, and substituted or unsubstituted C 6~50- Selected from aryl atoms, and more preferably a hydrogen atom, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl and substituted or unsubstituted C 6~30 - Selected from aryl atoms, and more preferably a hydrogen atom, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -Alkenyl), and substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 - Selected from aryl. More preferably, R5 to R8 are each independently a hydrogen atom, a substituted or unsubstituted C 1~70 -alkyl and substituted or unsubstituted C 6~70 - Selected from aryl atoms, more preferably a hydrogen atom, substituted or unsubstituted C 1~50 -alkyl and substituted or unsubstituted C 6~50- Selected from aryl atoms, and more preferably hydrogen atoms, substituted or unsubstituted C 1~30 -alkyl and substituted or unsubstituted C 6~30 - Selected from aryl atoms, and more preferably a hydrogen atom, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl) and substituted or unsubstituted C 6~20- Aryl (for example, C 8~20-R5 to R8 are selected from aryls. More preferably, each of R5 to R8 is independently selected from a hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. Most preferably, R5 to R8 are hydrogen atoms. Alternatively, two of R5, R6, and R7, or two of R6, R7, and R8, together with the atom to which they are bonded, form a substituted or unsubstituted cycloalkyl ring, a substituted or unsubstituted cycloalkenyl ring, or a substituted or unsubstituted heterocycloalkyl ring, such as alkylcyclohexa-2-ene-1-carboxylate or alkylcyclopentene-1-carboxylate.

[0055] R9 is an organic group having H or 1 to 70 carbon atoms. Preferably, R9 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl, substituted or unsubstituted C 2~70 -Alkynyl, substituted or unsubstituted C 1~70 - Heteroalkyl, substituted or unsubstituted C 3~70 -Cycloalkyl, substituted or unsubstituted C 3~70 -Cycloalkenyl, substituted or unsubstituted C 2~70 - Heterocycloalkyl, substituted or unsubstituted C 6~70 -aryl and substituted or unsubstituted C 4~70 -A heteroaryl compound, preferably H, substituted or unsubstituted C. 1~50 -alkyl, substituted or unsubstituted C 2~50 - Alkenyl, substituted or unsubstituted C 2~50 -Alkynyl, substituted or unsubstituted C 1~50 - Heteroalkyl, substituted or unsubstituted C 3~50 -Cycloalkyl, substituted or unsubstituted C 3~50 -Cycloalkenyl, substituted or unsubstituted C 2~50 - Heterocycloalkyl, substituted or unsubstituted C 6~50 - is aryl, and substituted or unsubstituted C 4~50-A heteroaryl, more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl, substituted or unsubstituted C 2~30 -Alkynyl, substituted or unsubstituted C 1~30 - Heteroalkyl, substituted or unsubstituted C 3~30 -Cycloalkyl, substituted or unsubstituted C 3~30 -Cycloalkenyl, substituted or unsubstituted C 2~30 - Heterocycloalkyl, substituted or unsubstituted C 6~30 -aryl and substituted or unsubstituted C 4~30 -A heteroaryl, more preferably H, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -alkenyl), substituted or unsubstituted C 2~20 -Alkinyl (for example, C 8~20 -alkynyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 3~20 -Cycloalkyl (e.g., C 8~20 -Cycloalkyl), substituted or unsubstituted C 3~20 -Cycloalkenyl (e.g., C 8~20 -Cycloalkenyl), substituted or unsubstituted C 2~20 - Heterocycloalkyl (e.g., C 8~20 -heterocycloalkyl), substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g., C 8~20 -heteroaryl) is preferred. Preferably, R9 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl, substituted or unsubstituted C 1~70 - Heteroalkyl, substituted or unsubstituted C 6~70 -aryl and substituted or unsubstituted C 4~70- Selected from heteroaryls, more preferably H, substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 - Alkenyl, substituted or unsubstituted C 1~50 - Heteroalkyl, substituted or unsubstituted C 6~50 -aryl and substituted or unsubstituted C 4~50 - Selected from heteroaryls, more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl, substituted or unsubstituted C 1~30 - Heteroalkyl, substituted or unsubstituted C 6~30 -aryl and substituted or unsubstituted C 4~30 - Selected from heteroaryls, more preferably H, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -alkenyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g., C 8~20 Selected from (heteroaryl). More preferably, R9 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl and substituted or unsubstituted C 6~70- Selected from aryl groups, more preferably H, substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 - Alkenyl and substituted or unsubstituted C 6~50- Selected from aryls, more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl and substituted or unsubstituted C 6~30- Selected from aryls, more preferably H, substituted or unsubstituted C 1~20 -alkyl (e.g., C8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -Alkenyl), and substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 - Selected from aryl(-). More preferably, R9 is H, substituted or unsubstituted C. 1~70 -alkyl and substituted or unsubstituted C 6~70 - Selected from aryls, more preferably H, substituted or unsubstituted C 1~50 -alkyl and substituted or unsubstituted C 6~50- Selected from aryls, more preferably H, substituted or unsubstituted C 1~30 -alkyl and substituted or unsubstituted C 6~30 - Selected from aryls, more preferably H, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl) and substituted or unsubstituted C 6~20- Aryl (for example, C 8~20- R9 is selected from aryls. More preferably, R9 is selected from H, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. Most preferably, R9 is selected from methyl, ethyl, and n-propyl.

[0056] Alternatively, R u Equation (XIII): [ka] (In the formula, the dashed line represents the bond of the carbonyl carbon of the ester portion of the ester-containing substrate in formula (I)) * It may be an organic group having a bond to )

[0057] R u If is an organic group of formula (XIII), then the ester-containing substrate of formula (I) includes β,γ unsaturated esters.

[0058] R 10 ~R12 Each of these is an organic group having either a hydrogen atom or 1 to 70 carbon atoms.

[0059] In the preferred method of the present invention, R 10 ~R 12 These are, independently, a hydrogen atom, a substituted or unsubstituted C atom, and each of these is independently a hydrogen atom. 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl, substituted or unsubstituted C 2~70 -Alkynyl, substituted or unsubstituted C 1~70 - Heteroalkyl, substituted or unsubstituted C 3~70 -Cycloalkyl, substituted or unsubstituted C 3~70 -Cycloalkenyl, substituted or unsubstituted C 2~70 - Heterocycloalkyl, substituted or unsubstituted C 6~70 -aryl and substituted or unsubstituted C 4~70 - Selected from heteroaryls, preferably substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 - Alkenyl, substituted or unsubstituted C 2~50 -Alkynyl, substituted or unsubstituted C 1~50 - Heteroalkyl, substituted or unsubstituted C 3~50 -Cycloalkyl, substituted or unsubstituted C 3~50 -Cycloalkenyl, substituted or unsubstituted C 2~50 - Heterocycloalkyl, substituted or unsubstituted C 6~50 -aryl and substituted or unsubstituted C 4~50 - Selected from heteroaryls, more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl, substituted or unsubstituted C 2~30 -Alkynyl, substituted or unsubstituted C 1~30 - Heteroalkyl, substituted or unsubstituted C 3~30 -Cycloalkyl, substituted or unsubstituted C 3~30 -Cycloalkenyl, substituted or unsubstituted C 2~30 - Heterocycloalkyl, substituted or unsubstituted C 6~30 -aryl and substituted or unsubstituted C 4~30- Selected from heteroaryls, and more preferably substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -alkenyl), substituted or unsubstituted C 2~20 -Alkinyl (for example, C 8~20 -alkynyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 3~20 -Cycloalkyl (e.g., C 8~20 -Cycloalkyl), substituted or unsubstituted C 3~20 -Cycloalkenyl (e.g., C 8~20 -Cycloalkenyl), substituted or unsubstituted C 2~20 - Heterocycloalkyl (e.g., C 8~20 -heterocycloalkyl), substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g., C 8~20 Selected from (heteroaryl). Preferably, R 10 ~R 12 These are, independently, a hydrogen atom, a substituted or unsubstituted C atom, and each of these is independently a hydrogen atom. 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl, substituted or unsubstituted C 1~70 - Heteroalkyl, substituted or unsubstituted C 6~70 -aryl and substituted or unsubstituted C 4~70 - Selected from heteroaryls, more preferably substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 - Alkenyl, substituted or unsubstituted C 1~50 - Heteroalkyl, substituted or unsubstituted C 6~50 -aryl and substituted or unsubstituted C 4~50 - Selected from heteroaryls, and more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl, substituted or unsubstituted C 1~30- Heteroalkyl, substituted or unsubstituted C 6~30 -aryl and substituted or unsubstituted C 4~30 - Selected from heteroaryls, and more preferably substituted or unsubstituted C 1~20 -(For example C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -alkenyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g., C 8~20 Selected from -heteroaryls). More preferably, R 10 ~R 12 These are, independently, a hydrogen atom, a substituted or unsubstituted C atom, and each of these is independently a hydrogen atom. 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl and substituted or unsubstituted C 6~70 - Selected from aryl atoms, more preferably a hydrogen atom, substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 - Alkenyl and substituted or unsubstituted C 6~50 - Selected from aryl atoms, and more preferably a hydrogen atom, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl and substituted or unsubstituted C 6~30 - Selected from aryl atoms, and more preferably a hydrogen atom, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -Alkenyl), and substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 - Selected from (aryl). More preferably, R 10 ~R 12 These are, independently, a hydrogen atom, a substituted or unsubstituted C atom, and each of these is independently a hydrogen atom. 1~70 -alkyl and substituted or unsubstituted C6~70 - Selected from aryl atoms, more preferably a hydrogen atom, substituted or unsubstituted C 1~50 -alkyl and substituted or unsubstituted C 6~50- Selected from aryl atoms, and more preferably hydrogen atoms, substituted or unsubstituted C 1~30 -alkyl and substituted or unsubstituted C 6~30 - Selected from aryl atoms, and more preferably a hydrogen atom, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl) and substituted or unsubstituted C 6~20 -aryl (for example, C 8~20 -Selected from aryl). More preferably, R 10 ~R 12 Each is independently selected from hydrogen atom, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. Most preferably, R 10 ~R 12 is a hydrogen atom. Or, R 10 , R 11 , and R 12 Two of these, together with the atoms to which they are bonded, form a substituted or unsubstituted cycloalkyl ring, a substituted or unsubstituted cycloalkenyl ring, or a substituted or unsubstituted heterocycloalkyl ring.

[0060] R 13 is an organic group having H or 1 to 70 carbon atoms. Preferably, R 13 H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl, substituted or unsubstituted C 2~70 -Alkynyl, substituted or unsubstituted C 1~70 - Heteroalkyl, substituted or unsubstituted C 3~70 -Cycloalkyl, substituted or unsubstituted C 3~70 -Cycloalkenyl and substituted or unsubstituted C 2~70 - Heterocycloalkyl, preferably H, substituted or unsubstituted C 1~50-alkyl, substituted or unsubstituted C 2~50 - Alkenyl, substituted or unsubstituted C 2~50 -Alkynyl, substituted or unsubstituted C 1~50 - Heteroalkyl, substituted or unsubstituted C 3~50 -Cycloalkyl, substituted or unsubstituted C 3~50 -Cycloalkenyl and substituted or unsubstituted C 2~50 - Heterocycloalkyl, more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl, substituted or unsubstituted C 2~30 -Alkynyl, substituted or unsubstituted C 1~30 - Heteroalkyl, substituted or unsubstituted C 3~30 -Cycloalkyl, substituted or unsubstituted C 3~30 -Cycloalkenyl and substituted or unsubstituted C 2~30 - Heterocycloalkyl, more preferably H, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -alkenyl), substituted or unsubstituted C 2~20 -Alkinyl (for example, C 8~20 -alkynyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 3~20 -Cycloalkyl (e.g., C 8~20 -Cycloalkyl), substituted or unsubstituted C 3~20 -Cycloalkenyl (e.g., C 8~20 -Cycloalkenyl), and substituted or unsubstituted C 2~20 - Heterocycloalkyl (e.g., C 8~20 -heterocycloalkyl) is preferred. 13 H, substituted or unsubstituted C 1~70 -alkyl and substituted or unsubstituted C 2~70 - Alkenyl, substituted or unsubstituted C 1~70 - Selected from heteroalkyl groups, more preferably H, substituted or unsubstituted C 1~50-alkyl, substituted or unsubstituted C 2~50 - Alkenyl and substituted or unsubstituted C 1~50 - Selected from heteroalkyls, and more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 - Alkenyl and substituted or unsubstituted C 1~30 - Selected from heteroalkyl groups, more preferably H, substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 -Alkenyl), and substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 Selected from (-heteroalkyl). More preferably, R 13 H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 - Alkenyl and substituted or unsubstituted C 6~70- Selected from aryl groups, more preferably H, substituted or unsubstituted C 1~50 -alkyl and substituted or unsubstituted C 2~50 - Selected from alkenyls, more preferably H, substituted or unsubstituted C 1~30 -alkyl and substituted or unsubstituted C 2~30- Selected from alkenyls, and more preferably substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 -alkyl), and substituted or unsubstituted C 2~20 -Alkenil (for example, C 8~20 - Selected from alkenyl). More preferably, R 13 H, substituted or unsubstituted C 1~70 -alkyl, more preferably substituted or unsubstituted C 1~50 - Selected from alkyl groups, more preferably H, substituted or unsubstituted C 1~30 - Selected from alkyl groups, and more preferably substituted or unsubstituted C 1~20 -alkyl (e.g., C 8~20 Selected from -alkyl). More preferably, R 13is selected from H, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. Most preferably, R 13 The compound is selected from methyl, ethyl, and n-propyl.

[0061] R 13 However, sp 2 It may be preferable that R9 is not a terminal CH2 group with hybridized carbon atoms. 2 It may be preferable that the terminal CH2 group does not have hybrid carbon atoms. R9 and R 13 However, sp 2 It may be preferable that the terminal CH2 group does not have hybridized carbon atoms.

[0062] In the ester-containing substrate of formula (I), R v R is an organic group having 1 to 70 carbon atoms. In the preferred method of the present invention, R v C is either substituted or non-substituted. 1~70 -alkyl, preferably substituted or unsubstituted C 1~50 -alkyl, more preferably substituted or unsubstituted C 1~30 -alkyl, more preferably substituted or unsubstituted C 1~20 -alkyl (for example, C 2~20 -Alkyl or C 3~20 Selected from -alkyl). Preferably, R v C is either substituted or non-substituted. 2~70 -alkyl, more preferably substituted or unsubstituted C 2~50 -alkyl, more preferably substituted or unsubstituted C 2~30 -alkyl, more preferably substituted or unsubstituted C 1~20 -alkyl, C 2~20 -Alkyl, or C 3~20 - Selected from alkyl groups. More preferably, R vR is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, and octyl. More preferably, v is selected from methyl, ethyl, n-propyl, or isopropyl. More preferably, R v is ethyl, n-butyl, or tert-butyl. Most preferably, R v It is ethyl.

[0063] In the preferred method of the present invention, the ester-containing substrate of formula (I) is an alkyl sorbate. Preferably, the alkyl sorbate is methyl sorbate, ethyl sorbate, n-propyl sorbate, iso-propyl sorbate, n-butyl sorbate, sec-butyl sorbate, or tert-butyl sorbate. More preferably, the alkyl sorbate is methyl sorbate or ethyl sorbate.

[0064] In the preferred method of the present invention, the ester-containing substrate of formula (I) is an alkyl trans-3-hexanoate. Preferably, the alkyl trans-3-hexanoate is methyl trans-3-hexanoate, ethyl trans-3-hexanoate, n-propyl trans-3-hexanoate, isopropyl trans-3-hexanoate, n-butyl trans-3-hexanoate, sec-butyl trans-3-hexanoate, isobutyl trans-3-hexanoate, or tert-butyl trans-3-hexanoate. More preferably, the alkyl trans-3-hexanoate is methyl trans-3-hexanoate or ethyl trans-3-hexanoate.

[0065] In the preferred method of the present invention, the ester-containing substrate of formula (I) is an alkylcis-3-hexanoate. Preferably, the alkylcis-3-hexanoate is methylcis-3-hexanoate, ethylcis-3-hexanoate, n-propylcis-3-hexanoate, isopropylcis-3-hexanoate, n-butylcis-3-hexanoate, sec-butylcis-3-hexanoate, isobutylcis-3-hexanoate, or tert-butylcis-3-hexanoate. More preferably, the alkylcis-3-hexanoate is methylcis-3-hexanoate or ethylcis-3-hexanoate.

[0066] In the preferred method of the present invention, the ester-containing substrate of formula (I) is an alkylsorbate, alkyltrans-3-hexanoate, or alkylcis-3-hexanoate as defined above.

[0067] Alcohol products When the ester-containing substrate of formula (I) is a monoester, the product of the method of the present invention is an alcohol of formula (II). In the preferred method of the present invention, the group R u The stereochemistry of the alkenyl group is the same for the ester-containing substrate of formula (I) and the product alcohol of formula (II).

[0068] In the preferred method of the present invention, the alcohol of formula (II) is trans,transhexa-2,4-dien-1-ol: [ka] That is the case.

[0069] Therefore, in a preferred embodiment of the present invention, the method is a method for producing an alcohol of formula (II), which is trans,trans-hexa-2,4-dien-1-ol, by hydrogenating an ester-containing substrate of formula (I).

[0070] In the most preferred method of the present invention, the ester-containing substrate of formula (I) is the alkyl sorbate as defined above, and the alcohol of formula (II) is trans,trans-hexa-2,4-dien-1-ol.

[0071] In the preferred method of the present invention, the alcohol of formula (II) is trans-hexa-3-en-1-ol: [ka] That is the case.

[0072] Therefore, in a preferred embodiment of the present invention, the method is a method for producing an alcohol of formula (II), which is trans-hexa-3-en-1-ol, by hydrogenating an ester-containing substrate of formula (I).

[0073] In the most preferred method of the present invention, the ester-containing substrate of formula (I) is the alkyl trans-3-hexanoate as defined above, and the alcohol of formula (II) is trans-hexa-3-en-1-ol.

[0074] In the preferred method of the present invention, the alcohol of formula (II) is cis-hexa-3-en-1-ol: [ka] That is the case.

[0075] Therefore, in a preferred embodiment of the present invention, the method is a method for producing an alcohol of formula (II), which is a cis-hexa-3-en-1-ol, by hydrogenating an ester-containing substrate of formula (I).

[0076] In the most preferred method of the present invention, the ester-containing substrate of formula (I) is the alkyl cis-3-hexanoate as defined above, and the alcohol of formula (II) is cis-hexa-3-en-1-ol.

[0077] base The bases of the present invention have a conjugate acid with a pKa of 4 to 15. While we do not wish to be bound by any theory, it is believed that using a base with a conjugate acid having a pKa of 4 to 15 minimizes or prevents the formation of enolate intermediates in the hydrogenation method of the present invention. It is hypothesized that the formation of such enolate intermediates may result in the reduction of alkenyl functional groups and the loss of regiochemistry of alkenes. Furthermore, it is believed that the formation of enolate intermediates may lead to the formation of other undesirable byproducts, such as those arising from cycloaddition reactions (e.g., Diels-Alder) or condensation reactions. In addition, the base is thought to play a role in the activation of the transition metal catalyst. Therefore, it is surprising that a base with a conjugate acid pKa of 4 to 15 functions to activate the transition metal catalyst of the present invention while simultaneously minimizing or preventing the formation of enolate intermediates.

[0078] In the preferred method of the present invention, the conjugate acid of the base has a pKa greater than 5, greater than 7, or greater than 9. In the preferred method of the present invention, the conjugate acid of the base has a pKa less than 14, less than 13, or less than 12. In the preferred method of the present invention, the conjugate acid of the base has a pKa of 5-14, 7-13, or 9-12, for example 9-11, for example about 10.

[0079] In the preferred method of the present invention, the base is a metal phosphate or metal carbonate, and the conjugate acid of the base has a pKa of 4 to 15. The metal carbonate or metal phosphate is preferably an alkali metal phosphate, an alkaline earth metal phosphate, an alkali metal carbonate, or an alkaline earth metal carbonate, and the conjugate acid of the base has a pKa of 4 to 15.

[0080] In a more preferred method of the present invention, the base is a metal phosphate, and the conjugate acid of the base has a pKa of 4 to 15. The metal phosphate is preferably an alkali metal phosphate or alkaline earth metal phosphate having a conjugate acid of 4 to 15 pKa. The metal phosphate is more preferably an alkali metal phosphate. The alkali metal phosphate is preferably lithium phosphate (Li3PO4), sodium phosphate (Na3PO4), potassium phosphate (K3PO4), or cesium phosphate (Cs3PO4). Most preferably, the base is an alkali metal phosphate with potassium phosphate (K3PO4).

[0081] In the preferred method of the present invention, the base exists in solid form.

[0082] In the preferred method of the present invention, the base is present in an amount of at least 30 mol%, preferably at least 35 mol%, more preferably at least 40 mol%, and even more preferably at least 45 mol%, relative to the total amount of the ester-containing substrate.

[0083] In the preferred method of the present invention, the base is present in an amount of 200 mol% or less relative to the total amount of the ester-containing substrate, and more preferably 125 mol% or less relative to the total amount of the ester-containing substrate.

[0084] In the preferred method of the present invention, the base is present in the range of 30 to 70 mol% of the total amount of the ester-containing substrate, more preferably in the range of 30 to 60 mol% of the total amount of the ester-containing substrate, and even more preferably in the range of 30 to 50 mol% of the total amount of the ester-containing substrate.

[0085] In the preferred method of the present invention, the base exists as a solid. In the preferred method of the present invention, the base is substantially insoluble in the ester-containing substrate of formula (I) and / or the alcohol of formula (II). In the preferred method of the present invention, the base is substantially insoluble in the solvent.

[0086] A preferred method of the present invention further includes a step of separating the base by filtration. The step of filtering out the base after filtration is performed after the hydrogenation of the ester-containing substrate of formula (I).

[0087] Using a base that is substantially insoluble in the ester-containing substrate of formula (I) and / or the alcohol and / or solvent of formula (II) has the advantage that the reaction product can be easily separated, for example, from the alcohol of formula (II). Therefore, bases such as potassium phosphate (K3PO4), which are insoluble in organic solvents such as toluene and THF, have the further advantage of being easily separated, for example, by filtration.

[0088] solvent In the preferred method of the present invention, the method is carried out in the absence of a solvent. This has the advantage of making the method easier and less expensive to implement.

[0089] In another preferred method of the present invention, the method is carried out in the presence of a solvent.

[0090] Preferably, the solvent is selected from alcohol, toluene, THF, and Me-THF. More preferably, the solvent is selected from toluene, THF, and Me-THF. Most preferably, the solvent is selected from toluene and THF.

[0091] In the preferred method of the present invention, the solvent is present in an amount of 10 to 100% by volume based on the total volume of the ester-containing substrate, preferably 15 to 95% by volume based on the total volume of the ester-containing substrate, and more preferably 20 to 90% by volume based on the total volume of the ester-containing substrate (for example, 50% by volume based on the total volume of the ester-containing substrate).

[0092] In the preferred method of the present invention, the volume ratio of the solvent to the ester-containing substrate is 1:1 or less, preferably 1:2 or less.

[0093] In the preferred method of the present invention, the volume ratio of the solvent to the ester-containing substrate is in the range of 1:2 to 1:1, preferably in the range of 1:2 to 1:1.5.

[0094] In the preferred method of the present invention, the method is carried out in the presence of two or more solvents. The preferred solvents are as described above.

[0095] In another preferred method of the present invention, the method is carried out in the presence of a first solvent and a second solvent.

[0096] In the preferred method of the present invention, the first solvent is selected from toluene, THF, and Me-THF. In the preferred method of the present invention, the second solvent is an alcohol, preferably methanol or ethanol.

[0097] In a particularly preferred method of the present invention, the first solvent is toluene, and the second solvent is an alcohol, preferably methanol or ethanol.

[0098] In an alternative and particularly preferred method of the present invention, the first solvent is THF, and the second solvent is an alcohol, preferably methanol or ethanol.

[0099] In the preferred method of the present invention, the first solvent is present in an amount of 10 to 100% by volume, preferably 15 to 95% by volume, and more preferably 20 to 90% by volume (for example, 50% by volume) based on the total volume of the ester-containing substrate.

[0100] In the preferred method of the present invention, the volume ratio of the first solvent to the ester-containing substrate is 1:1 or less, preferably 1:2 or less.

[0101] In the preferred method of the present invention, the volume ratio of the first solvent to the ester-containing substrate is in the range of 1:2 to 1:1, preferably in the range of 1:2 to 1:1.5.

[0102] In the preferred method of the present invention, the second solvent is present in an amount of 1 to 15% by volume based on the total volume of the ester-containing substrate, preferably 1 to 10% by volume based on the total volume of the ester-containing substrate, preferably 1 to 7.5% by volume based on the total volume of the ester-containing substrate, and more preferably 1 to 5% by volume based on the total volume of the ester-containing substrate.

[0103] In a preferred method of the present invention, the first solvent is present in an amount of 10 to 100% by volume based on the total volume of the ester-containing substrate, and the second solvent is present in an amount of 1 to 10% by volume based on the total volume of the ester-containing substrate, preferably the first solvent is present in an amount of 15 to 95% by volume based on the total volume of the ester-containing substrate, and the second solvent is present in an amount of 1 to 7.5% by volume based on the total volume of the ester-containing substrate, and more preferably the first solvent is present in an amount of 20 to 90% by volume based on the total volume of the ester-containing substrate, and the second solvent is present in an amount of 1 to 5% by volume based on the total volume of the ester-containing substrate.

[0104] by-product The method of the present invention has the remarkable advantage of producing less unwanted by-products.

[0105] As described above, in conventional methods and / or methods using strong bases (for example, those whose conjugate acid has a pKa greater than 15, such as metal alkoxides), unwanted by-products may be formed.

[0106] Unwanted by-products typically include wax esters, saturated alcohols, saturated esters, and hemiacetals. While we do not wish to be bound by any theory, the formation of these unwanted by-products is thought to be due to the formation of enolate intermediate compounds. Therefore, it is thought that the method of the present invention minimizes or eliminates the formation of enolate intermediates, resulting in the formation of smaller amounts of unwanted by-products.

[0107] temperature The method of the present invention may be carried out at a temperature in the range of 20 to 150°C. In a preferred method of the present invention, the method may be carried out at a temperature in the range of 40 to 90°C, more preferably 40 to 85°C, even more preferably 50 to 85°C, even more preferably 50 to 80°C, even more preferably 55 to 75°C, and most preferably 60 to 75°C (for example, about 70°C).

[0108] The preferred method of the present invention is carried out at relatively low temperatures. Surprisingly, it has been found that using temperatures within the preferred range described above results in less formation of undesirable byproducts while maintaining a good reaction rate compared to using higher temperatures.

[0109] In a particularly preferred embodiment of this method, the solvent is toluene, and the method is carried out at a temperature in the range of 40 to 90°C, more preferably 45 to 85°C, even more preferably 50 to 85°C, even more preferably 50 to 80°C, even more preferably 55 to 75°C, and most preferably 60 to 75°C (e.g., about 70°C).

[0110] It is surprising that, when toluene is the solvent, hydrogen gas uptake in the hydrogenation process improves at temperatures lower than toluene's atmospheric pressure boiling point (approximately 110°C).

[0111] pressure The preferred method of the present invention is carried out at a pressure of at least 5 bar, more preferably at least 10 bar, even more preferably at least 20 bar, even more preferably at least 30 bar, even more preferably at least 40 bar, and most preferably at least 50 bar.

[0112] The preferred method of the present invention is carried out at a pressure in the range of 5 to 100 bar, more preferably in the range of 10 to 95 bar, even more preferably in the range of 20 to 90 bar, even more preferably in the range of 25 to 70 bar, and most preferably in the range of 30 to 50 bar.

[0113] Duration The preferred method of the present invention is carried out over a period of time of 1 to 24 hours, more preferably 2 to 20 hours, even more preferably 3 to 18 hours, and most preferably 4 to 16 hours.

[0114] S / C-substrate / catalyst In the preferred method of the present invention, the substrate / catalyst load is 500 / 1 or more, preferably 650 / 1 or more, more preferably 750 / 1 or more, and even more preferably 850 / 1 or more. In the preferred method of the present invention, the substrate / catalyst load is 50,000 / 1 or less, preferably 30,000 / 1 or less, more preferably 20,000 / 1 or less, and even more preferably 10,000 / 1 or less. For example, in the preferred method of the present invention, the substrate / catalyst load is 500 / 1 or more and 50,000 / 1 or less, preferably 650 / 1 or more and 30,000 / 1 or less, more preferably 750 / 1 or more and 20,000 / 1 or less, and even more preferably 1,000 / 1 or more and 10,000 / 1 or less, for example 5,000 / 1.

[0115] transition metal catalyst The method of the present invention uses a transition metal catalyst. The transition metal catalyst may be pre-formed or formed in situ during the esterification hydrogenation reaction. Preferably, the transition metal catalyst is pre-formed. Alternatively, the transition metal catalyst is formed in situ during the esterification hydrogenation reaction.

[0116] In the preferred method of the present invention, the transition metal in the transition metal catalyst is a transition metal of Group 6, Group 7, Group 8, or Group 9. More preferably, the transition metal in the transition metal catalyst is a transition metal of Group 7, Group 8, or Group 9. Even more preferably, the transition metal in the transition metal catalyst is a transition metal of Group 8.

[0117] In the preferred method of the present invention, the transition metal in the transition metal catalyst is selected from Mo, Mn, Fe, Ru, Co, and Os. More preferably, the transition metal in the transition metal catalyst is selected from Ru and Os. Most preferably, the transition metal in the transition metal catalyst is Ru.

[0118] In a preferred method of the present invention, the transition metal catalyst used in the method of the present invention includes a tridentate ligand.

[0119] In the preferred method of the present invention, the transition metal catalyst is a tridentate ligand having formula (III). [ka] (In the formula, X is -SR a , -OR a ,-CR a , -NR a R b ,-PR a R b ,-P(=O)R a R b ,-OPR a R b , and -NHPR a R b Selected from; R 1 and R x These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20- Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls, or R 1 and R 3a and R 3bOne of the two, or R x and R 3a and R 3b One of them forms a ring with the atom to which they are bonded; Alternatively, X is a heteroatom, and R x If R does not exist, 1 Together with it, it forms a heterocycle that is optionally substituted; Y is -SR a , -OR a ,-CR a , -NR a R b ,-PR a R b ,-P(=O)R a R b ,-OPR a R b , and -NHPR a R b Selected from; R 2 and R y These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls, or R 2 and R 4a and R 4b One of the two, or R y and R 4a and R 4b One of them forms a ring with the atom to which they are bonded; Alternatively, Y is a heteroatom, and R y If R does not exist, 2 Together with it, it forms a heterocycle that is optionally substituted; R 3a、 R 3b , R 4a and R 4b These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls, or R 3a and R 4a and R 4b One of the two, or R 3b and R 4a and R 4b One of them forms a heteroring with the atom to which they are bonded; R5 is hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Each m and n is independently 1 or 2; and R a and R b If present, each independently comprises hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or X and / or Y are -NR a R b ,-PR a R b ,-OPR a R b , or -NHPR a R b If R a and R b It includes (which, together with the heteroatoms to which they are bonded, form a heterocycle).

[0120] In the trident ligand of formula (III), X is preferably -SR a ,-CR a , -NR a R b ,-PR a R b , and -NHPR a R b Selected from. More preferably, X is -SR a ,-PR a R b , and -NHPR a R b Selected from. More preferably, X is -SR a and -PR a R b Selected from: Most preferably, X is -SR a That is the case.

[0121] In the trident ligand of equation (III), R 1 and R x Each is preferably independently hydrogen, substituted or unsubstituted C1~20 -alkyl, substituted or unsubstituted C 1~20- Heteroalkyl and substituted or unsubstituted C 3~20- Selected from cycloalkyl groups. More preferably, R 1 and R x These are, independently, hydrogen and substituted or unsubstituted C. 1~20 -Selected from alkyl. More preferably, R 1 and R x These are hydrogen atoms, respectively.

[0122] In another preferred tridentate ligand of equation (III), R x It does not exist, X is a heteroatom, and R 1 Together with, it forms a heterocycle that is optionally substituted. More preferably, R x It does not exist, X is a heteroatom, and R 1 Together with these, they form a heteroaromatic ring that is optionally substituted. More preferably, the optionally substituted heteroaromatic ring is an optionally substituted nitrogen-containing heteroaromatic ring. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl. Most preferably, the optionally substituted nitrogen-containing heteroaromatic ring is pyridinyl.

[0123] In the trident ligand of formula (III), Y is preferably -SR a ,-CR a , -NR a R b ,-PR a R b , and -NHPR a R bSelected from. More preferably, Y is -SR a ,-PR a R b , and -NHPR a R b Selected from. More preferably, Y is -SR a and -PR a R b Selected from: Most preferably, Y is -SR a That is the case.

[0124] In the trident ligand of equation (III), R 2 and R y Each of these is independently preferably hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl and substituted or unsubstituted C 3~20 - Selected from cycloalkyl. More preferably, R 2 and R y These are, independently, hydrogen and substituted or unsubstituted C. 1~20 -Selected from alkyl. More preferably, R 2 and R y These are hydrogen atoms, respectively.

[0125] In another preferred tridentate ligand of formula (III), Y is a heteroatom, and R y If R does not exist, 2 Together with, they form a heterocycle that can be optionally substituted. More preferably, Y is a heteroatom, and R y If R does not exist, 2Together with these, they form a heteroaromatic ring that is optionally substituted. More preferably, the optionally substituted heteroaromatic ring is an optionally substituted nitrogen-containing heteroaromatic ring. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl. Most preferably, the optionally substituted nitrogen-containing heteroaromatic ring is pyridinyl.

[0126] In the trident ligand of equation (III), R 3a , R 3b , R 4a , and R 4b Each of these is independently preferably hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl and substituted or unsubstituted C 3~20 - Selected from cycloalkyl. More preferably, R 3a , R 3b , R 4a , and R 4b These are, independently, hydrogen and substituted or unsubstituted C. 1~20 -Selected from alkyl. More preferably, R 3a , R 3b , R 4a , and R 4b These are hydrogen atoms, respectively.

[0127] In another preferred tridentate ligand of formula (III), R 3a and R 4a and R 4b One of the two, or R 3b and R 4a and R 4bOne of the atoms forms a heteroring with the atom to which they are bonded. Preferably, the heteroring is a six-membered heteroring.

[0128] In the trident ligand of equation (III), R 5 Preferably, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl and substituted or unsubstituted C 3~20 - Selected from cycloalkyl. More preferably, R 5 This is hydrogen and substituted or unsubstituted C 1~20 -Selected from alkyl. More preferably, R 5 It is hydrogen.

[0129] In the tridentate ligand of formula (III), m and n are preferably 1.

[0130] In the trident ligand of equation (III), R a and R b If present, each is preferably independently hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls. More preferably, R a and R b If present, each independently comprises hydrogen, substituted or unsubstituted C 1~20 -alkyl (e.g., C 1~10 -alkyl) and substituted or unsubstituted C 6~20 - Selected from the alphabet. Particularly preferred C 1~20 -Examples of alkyl groups include ethyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl and hexyl, more preferably methyl, ethyl, isopropyl, tert-butyl, and even more preferably ethyl. Preferred C 6~20-Examples of aryl groups include phenyl, tolyl, xylyl, and methoxyphenyl, more preferably phenyl.

[0131] In another preferred tridentate ligand of formula (III), X and / or Y are -NR a R b ,-PR a R b ,-OPR a R b or -NHPR a R b If R a and R b These, along with the heteroatoms to which they are bonded, form a heterocycle.

[0132] In the preferred method of the present invention, the transition metal catalyst comprises a tridentate ligand having formula (III), During the ceremony, X is -SR a ,-CR a , -NR a R b ,-PR a R b , and -NHPR a R b Selected from; R 1 and R x These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Alternatively, X is a heteroatom, and R x If R does not exist, 1Together with it, it forms a heteroaromatic ring that is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring; Y is -SR a ,-CR a , -NR a R b ,-PR a R b , and -NHPR a R b Selected from; R 2 and R y These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Alternatively, Y is a heteroatom, and R y If R does not exist, 2 Together with it, it forms a heteroaromatic ring that is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring; R 3a , R 3b , R 4a , R 4b and R 5 These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20-Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Each m and n is independently 1 or 2; and R a and R b If present, each independently comprises hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or X and / or Y are -NR a R b ,-PR a R b or -NHPR a R b If R a and R b These, along with the heteroatoms to which they are bonded, form a heterocycle.

[0133] In the preferred method of the present invention, the transition metal catalyst comprises a tridentate ligand having formula (III), During the ceremony, X is -SR a ,-PR a R b , and -NHPR a R b Selected from; R 1 and R x These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20- Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Alternatively, X is a heteroatom, and R x If R does not exist, 1 Together with these, they form a heteroaromatic ring that is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl; Y is -SR a ,-PR a R b , and -NHPR a R b Selected from; R 2 and R y These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Alternatively, Y is a heteroatom, and R y If R does not exist, 2 Together with these, they form a heteroaromatic ring which is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl; R 3a , R 3b , R 4a , R 4b and R 5 These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Each m and n is independently 1 or 2; and R a and R b If present, each independently comprises hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20- Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or X and / or Y are -PR a R b or -NHPR a R b If R a and R b These, along with the heteroatoms to which they are bonded, form a heterocycle.

[0134] In the preferred method of the present invention, the transition metal catalyst comprises a tridentate ligand having formula (III), During the ceremony, X is -SR a and -PR a R b Selected from; R 1 and R x These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Alternatively, X is a heteroatom, and R x If R does not exist, 1 Together with a heteroaromatic ring that is optionally substituted, the heteroaromatic ring is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl; Y is -SR a and -PR a R b Selected from; R 2 and R y These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Alternatively, Y is a heteroatom, and R y If R does not exist, 2 Together with these, they form a heteroaromatic ring that is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl; R 3a , R 3b , R 4a , R 4b and R 5 These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Each m and n is independently 1 or 2; and Ra and R b is, when present, each independently hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or when X and / or Y is -PR a R b is, R a and R b form a heterocycle together with the heteroatom to which they are attached.

[0135] In a preferred method of the present invention, the transition metal catalyst comprises a tridentate ligand having the formula (III), wherein X is -SR a is; R 1 and R x are each independently hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 ed C -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; Y is -SR a is; R2 and R y These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; R 3a , R 3b , R 4a , R 4b and R 5 These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Each m and n is independently 1 or 2; and R a These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C3~20 - cycloalkyl, substituted or unsubstituted C 3~20 - cycloalkenyl, substituted or unsubstituted C 2~20 - heterocycloalkyl, substituted or unsubstituted C 6~20 - aryl, and substituted or unsubstituted C 4~20 - heteroaryl.

[0136] Preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III), wherein, [[ID=...]] X is -SR a ; R 1 and R x are each independently hydrogen, substituted or unsubstituted C 1~20 - alkyl, substituted or unsubstituted C 1~20 - heteroalkyl, and substituted or unsubstituted C 3~20 - cycloalkyl; Y is -SR a ; R 2 and R y are each independently hydrogen, substituted or unsubstituted C 1~20 - alkyl, substituted or unsubstituted C 1~20 - heteroalkyl, and substituted or unsubstituted C 3~20 [[ID=...]] 3a 、R 3b 、R 4a 、R 4b and R 5 are each independently hydrogen, substituted or unsubstituted C 1~20 - alkyl, substituted or unsubstituted C 1~20 - heteroalkyl, and substituted or unsubstituted C 3~20 - cycloalkyl; each m and n is independently 1 or 2; and R a are each independently hydrogen, substituted or unsubstituted C 1~20 - alkyl, substituted or unsubstituted C 1~20 - heteroalkyl, and substituted or unsubstituted C 3~20 - cycloalkyl.​​​

[0137] More preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), wherein, X is -SR a and; R 1 and R x These are, independently, hydrogen and substituted or unsubstituted C. 1~20 -Selected from alkyl groups; Y is -SR a and; R 2 and R y These are, independently, hydrogen and substituted or unsubstituted C. 1~20 -Selected from alkyl groups; R 3a , R 3b , R 4a , R 4b and R 5 These are, independently, hydrogen and substituted or unsubstituted C. 1~20 -Selected from alkyl groups; Each m and n is independently 1 or 2; and R a These are, independently, hydrogen and substituted or unsubstituted C. 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl and substituted or unsubstituted C 3~20 - Selected from cycloalkyl.

[0138] More preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), wherein, X and Y are -SR, respectively. a and; R 1 , R x , R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 These are each hydrogen; m and n are each 1; and R a These are, independently, substituted or non-substituted C.1~20 -alkyl, preferably C 1~10 It is alkyl.

[0139] More preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), wherein, X and Y are -SEt, respectively; R 1 , R x , R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 Each of them is hydrogen; and m and n are both 1.

[0140] In another preferred method of the present invention, the transition metal catalyst comprises a tridentate ligand having formula (III), where, X is a heteroatom, and R 1 Together with R x If it is not present, it forms a heteroaromatic ring that is optionally substituted; Y is -PR a R b and; R 2 and R y These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; R 3a , R 3b , R 4a , R4b and R 5 These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Each m and n is independently 1 or 2; and R a and R b These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or R a and R b These, along with the heteroatoms to which they are bonded, form a heterocycle.

[0141] Preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), where, X is a nitrogen atom, and R x If R does not exist, 1Together with it, it forms a heteroaromatic ring that is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring; Y is -PR a R b and; R 2 and R y These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl and substituted or unsubstituted C 3~20 - Selected from cycloalkyl groups; R 3a , R 3b , R 4a , R 4b and R 5 These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 3~20 - Selected from cycloalkyl groups; Each m and n is independently 1 or 2; and R a and R b These are, independently, substituted or non-substituted C. 1~20 -alkyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls.

[0142] More preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), wherein, X is a nitrogen atom, and R x If R does not exist, 1Together with these, they form a heteroaromatic ring that is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 These are each hydrogen; Each m and n is 1; and R a and R b These are, independently, substituted or non-substituted C. 1~20 -alkyl and substituted or unsubstituted C 6~20 - Selected from the list.

[0143] More preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), wherein, X is a nitrogen atom, and R x If R does not exist, 1 Together with these, they form a heteroaromatic ring that is optionally substituted, and the heteroaromatic ring is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b , and R 5 These are each hydrogen; Each m and n is 1; and R a and Rb Each of these is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, phenyl, tolyl, xylyl, and methoxyphenyl.

[0144] More preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), wherein, X is a nitrogen atom, and R x If R does not exist, 1 Together with it, it forms a pyridinyl ring that can be optionally substituted; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 These are each hydrogen; Each m and n is 1; and R a and R b Each of these is independently selected from methyl, ethyl, isopropyl, tert-butyl, phenyl, tolyl, xylyl, and methoxyphenyl.

[0145] More preferably, the transition metal catalyst comprises a tridentate ligand having formula (III), wherein, X is a nitrogen atom, and R x If R does not exist, 1 Together with it, it forms a pyridinyl ring that can be optionally substituted; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 These are each hydrogen; Each m and n is 1; and R aand R b These are phenyl compounds, respectively.

[0146] In the preferred method of the present invention, the transition metal catalyst has formula (IV) or formula (V). [M(L 1 )(L 2 ) d (IV) [M(L 1 )(L 2 ) d ]W (V) (In the formula, M is a transition metal; L 1 is a tridentate ligand as defined herein; L 2 These are ligands that may be the same or different; d is 1, 2 or 3; and W is a non-coordinating anion ligand.

[0147] In a preferred method of the present invention, M is a transition metal of Group 6, Group 7, Group 8, or Group 9. More preferably, M is a transition metal of Group 7, Group 8, or Group 9. Even more preferably, M is a transition metal of Group 8.

[0148] In the preferred method of the present invention, M is a transition metal selected from Mo, Mn, Fe, Ru, Co, and Os. More preferably, M is a transition metal selected from Ru and Os. Most preferably, M is Ru.

[0149] In the preferred method of the present invention, d is 3.

[0150] As will be understood by those skilled in the art, each L 2 L may be a monosect ligand or a polysect ligand, however, 2 The ligand combinations are permitted by the rules of valence. In the preferred method of the present invention, each L 2 is a single-seat ligand. Preferably, each L 2L is independently a neutral monodentate ligand or an anionic monodentate ligand. In the preferred method of the present invention, each L 2 R' is independently selected from -H, -CO, -CN, -P(R')3, -As(R')3, -CR', -OR', -O(C=O)R', -NR'2, halogens (e.g., -Cl, -Br, -I), and solvents, where each R' is independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. Preferably, each L 2 These are independently selected from -H, -CO, -P(R')3, and halogens. More preferably, each L 2 L is independently selected from -CO, -PPh3, and -Cl. 2 If the solvent is [unspecified], the solvent is preferably selected from THF, Me-THF, MeCN, H2O, and alcohols (e.g., methanol, ethanol, isopropanol, etc.).

[0151] In the transition metal catalyst of formula (V), W is a non-coordinating anionic ligand. "Non-coordinating anionic ligand" means that the anionic ligand is forced to bond to the outer sphere of the metal center. Therefore, the anionic ligand dissociates from the metal center. This is in contrast to neutral complexes where the anionic ligand bonds to the metal within the coordination sphere. Anionic ligands can generally be identified as non-coordinating by analyzing the X-ray crystal structure of the cation complex. Preferably, W is a triflate (i.e., TfO). - or CF3SO3 - ), tetrafluoroborate (i.e., -BF4), hexafluoroantimonate (i.e., -SbF6), hexafluorophosphate (PF6) - ), [B[3,5-(CF3)2C6H3]4] - ([BArF4] - ), halides (e.g., Cl - , Br - , I -) and mesylate (MsO - or MeSO3 - Selected from the group consisting of ).

[0152] Preferably, the transition metal catalyst is a transition metal catalyst of formula (IV).

[0153] Alternatively, the transition metal catalyst is the transition metal catalyst of formula (V).

[0154] In the preferred method of the present invention, the transition metal catalyst is [ka] A transition metal catalyst selected from, for example, [ka] That is the case.

[0155] In the preferred method of the present invention, the transition metal catalyst is [ka] That is the case.

[0156] In the preferred method of the present invention, the transition metal catalyst is Ru-SNS, Ru-SNN, or Ru-PNN. More preferably, the transition metal catalyst is Ru-SNS or Ru-PNN.

[0157] In the preferred method of the present invention, the transition metal catalyst is [ka] That is the case.

[0158] In a preferred method of the present invention, the transition metal catalyst used in the method of the present invention includes a bidentate ligand.

[0159] In the preferred method of the present invention, the transition metal catalyst comprises a bidentate ligand having formula (VI). [ka] (In the formula, X' is -NHR ax and; Y' is -SR ax , -OR ax ,-CR ax , -NR ax R bx ,-PR ax R bx ,-P(=O)R ax R bx ,-OPR ax R bx , and -NHPR ax R bx Selected from; R 8a , R 8b , R 9a and R 9b These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; p is either 1 or 2; and R ax and R bx If present, each independently comprises hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20-Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or X' and / or Y' are -NR ax R bx ,-PR ax R bx ,-OPR ax R bx , or -NHPR ax R bx If R ax and R bx These, along with the heteroatoms to which they are bonded, form a heterocycle.

[0160] In the preferred method of the present invention, the transition metal catalyst has formula (VII) or formula (VIII). [M(L 1 ) e (L 2 ) f (VII) [M(L 1 ) e (L 2 ) f ]W (VIII) (In the formula, M is a transition metal; L 1 These are the aforementioned bidentate ligands, which may be the same or different; L 2 These are ligands that, if present, may be identical or different; e is 1 or 2, and if e is 1, f is 2, 3 or 4, and if e is 2, f is 0, 1 or 2; and W is a non-coordinating anion ligand. M, L 2 And W are generally as described above.

[0161] In a preferred method of the present invention, the transition metal catalyst used in the method of the present invention includes a tetradentate ligand.

[0162] In the preferred method of the present invention, the transition metal catalyst comprises a tetradentate ligand having formula (IX). [ka] (In the formula, Q is -SR ay , -OR ay ,-CR ay , -NR ay R by ,-PR ay R by ,-P(=O)R ay R by ,-OPR ay R by , and -NHPR ay R by Selected from; R 15 and R q These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Alternatively, Q is a heteroatom, and R q If R does not exist, 15 Together with it, it forms a heterocycle that is optionally substituted; W is S, O, NR a , and PR a Selected from; R 16 , R w and R z These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20- Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or R 16 R w If R does not exist, z Together with it, it forms a heterocycle that is optionally substituted; Z is -SR ay , -OR ay ,-CR ay , -NR ay R by ,-PR ay R by ,-P(=O)R ay R by ,-OPR ay R by , and -NHPR ay R by Selected from; R 10a , R 10b , R 11a and R 11b These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or R10a and R 11a and R 11b One of the two, or R 10b and R 11a and R 11b One of them forms a heteroring with the atom to which they are bonded; R 12a , R 12b , R 13a , R 13b and R 14 These are, independently, hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; Each q and r is independently 1 or 2; s is 0, 1 or 2; and R ay and R by If present, each independently comprises hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 - Alkenyl, substituted or unsubstituted C 2~20 -Alkynyl, substituted or unsubstituted C 1~20 - Heteroalkyl, substituted or unsubstituted C 1~20 - HPLC, substituted or unsubstituted C 3~20 -Cycloalkyl, substituted or unsubstituted C 3~20 -Cycloalkenyl, substituted or unsubstituted C 2~20 - Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl and substituted or unsubstituted C 4~20 - Selected from heteroaryls; or Q and / or Z are -NR ay Rby ,-PR ay R by ,-OPR ay R by , or -NHPR ay R by In the case of R ay and R by These, along with the heteroatoms to which they are bonded, form a heterocycle.

[0163] In the preferred method of the present invention, the transition metal catalyst is of formula (X) or formula (XI) [M(L 1 )(L 2 ) g ] (X) [M(L 1 )(L 2 ) g ]W (XI) (In the formula, M is a transition metal; L 1 is a tetradentate ligand as defined herein; L 2 These are ligands that, if present, may be identical or different; g is 0, 1 or 2; and W has a non-coordinating anion ligand. M, L 2 And W are generally as described above.

[0164] In the preferred method of the present invention, the transition metal catalyst is removed from the reaction mixture by a precipitation step using a cosolvent.

[0165] In another preferred method of the present invention, the transition metal catalyst is removed from the reaction mixture by distillation of the product.

[0166] In another preferred method of the present invention, the transition metal catalyst is removed from the reaction mixture by crystallization of the product.

[0167] In another preferred method of the present invention, the transition metal catalyst is removed from the reaction mixture using a metal scavenger.

[0168] In the preferred method of the present invention, the process is a flow process. Preferably, the process is a flow process in which excess base is recycled or reused. The base may be recycled or reused once, twice, three times, or more times.

[0169] The present invention will be further illustrated hereby by the following non-limiting embodiments.

[0170] Examples The catalysts Ru-SNS, Ru-PNN, SNS-RuHCl(CO), and PNN-RuHCl(CO) were commercially available from Johnson Matthey PLC and used as supplied.

[0171] Ru-MACHO-BH was available from Strem Chemicals and was used as supplied.

[0172] OsPNN(N) was available from Merck and was used as supplied.

[0173] K3PO4 and NaOEt are available from Acros Organics, Alfa Aesar, Fischer Scientific, and Merck. K3PO4 was stored in a glove box filled with argon gas until use. The liquid reagents and anhydrous solvent were stored under nitrogen and transferred to reaction vials using standard air-sensitive handling procedures.

[0174] The reaction was carried out using a 10 mL reaction vial in a Biotage Endeavour multi-well pressurized reaction system.

[0175] General Test Procedures The transition metal catalyst was added to the reaction vial along with the base in a glove box filled with argon. Anhydrous solvent was injected into the reaction vial, followed by the injection of the substrate via syringe. The reactants were sealed in a Biotage Endeavour multiwell pressurized reaction system. The reaction vial was purged five times with nitrogen and once with hydrogen, then sealed and heated to the desired reaction temperature. The reaction vessel was pressurized to 400 psi with hydrogen and stirred at a constant speed of 450-600 rpm. Each reaction was carried out for 16 hours. The reaction mixture was analyzed by gas chromatography (GC) using ethanol as the solvent.

[0176] Measurement method Gas chromatography (GC) measurements were performed using a Varian 3900 or 3800 gas chromatograph system. Unless otherwise specified, reaction conversion rates were determined by GC analysis.

[0177] Example 1: Hydrogenation of esters The above general procedure applies to the following ester-containing substrate: [ka] This was implemented against.

[0178] The desired product from substrate 1 and substrate 2 is the corresponding alcohol of formula (II), i.e.: [ka] That was the case.

[0179] The bases are a "weak base" (e.g., K3PO4) obtained by the method of the present invention and a "strong base" obtained by a method not obtained by the method of the present invention (e.g., NaOEt or NaO t It was changed between Bu)

[0180] Various reaction conditions were varied, including the amount of base (relative to the substrate), the substrate-to-transition metal catalyst ratio, the reaction temperature, the solvent system, and the transition metal catalyst itself. The transition metal catalysts used in the examples are as defined above. The results of gas chromatography analysis show the conversion rate to the corresponding alcohol of formula (II), the molar amount of unreacted starting material, the molar amount of saturated starting material (i.e., when the double bonds of the starting material decreased but the ester did not), and the molar amount of waxy ester byproduct. These experimental results are summarized in Tables 1 to 3 below. Examples 1 to 10 and 17 to 48 are according to the present invention, while Examples 11 to 16 and 49 to 56 are comparative examples. [Table 1] [Table 2] [Table 3]

[0181] The examples demonstrate that the method of the present invention can achieve excellent conversion of formula (II) to a desired alcohol with minimal byproduct formation. In particular, low catalytic loads can be used in a variety of solvent systems.

[0182] In contrast to using the base according to the present invention, when using a "strong" base such as NaOEt or NaotBu, the conversion of formula (II) to the desired alcohol is insufficient. Instead, by-products are formed, such as those with reduced alkene bonds, those containing waxy ester substances, or other unidentified by-products.

Claims

1. A method for producing an alcohol of formula (II) by hydrogenating an ester-containing substrate of formula (I), 【Chemistry 1】 The method comprises treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen, wherein the transition metal in the transition metal catalyst is Ru. The ester-containing substrate of formula (I) includes α,β-γ,δ unsaturated esters or β,γ unsaturated esters; R ｕ This is an organic group having 3 to 70 carbon atoms, however, R ｕ The carbonyl carbon of the ester ( ＊ Conditional on the bond forming an α,β-γ,δ unsaturated ester or β,γ unsaturated ester of formula (I); R ｖ is an organic group having 1 to 70 carbon atoms; and The method wherein the conjugate acid of the base has a pKa of 4 to 15.

2. R ｕ However, equation (XII): 【Chemistry 2】 (In the formula, the dashed line represents the bond between the carbonyl carbon of the ester portion of the ester-containing substrate in formula (I)) ＊ This indicates a binding to ); R ５ ~R ８ Each is independently an organic group having a hydrogen atom or 1 to 70 carbon atoms, and R ９ is an organic group having an organic group having H or an organic group having 1 to 70 carbon atoms), the method according to claim 1.

3. R ｕ However, equation (XIII): 【Transformation 3】 (In the formula, the dashed line represents the bond between the carbonyl carbon of the ester portion of the ester-containing substrate in formula (I)) ＊ This indicates a binding to ); R １０ ~R １２ Each is independently an organic group having a hydrogen atom or 1 to 70 carbon atoms, and R １３ The method according to claim 1, wherein is an organic group having H or an organic group having 1 to 70 carbon atoms.

4. R ｕ The method according to claim 1, wherein the organic group is an organic group having formula (XII) or formula (XIII) as defined in claim 2 or claim 3.

5. The method according to claim 1, wherein the ester-containing substrate of formula (I) is an alkylsorbate or an alkyl trans-3-hexanoate.

6. The method according to any one of claims 1 to 3, 5, wherein the alcohol of formula (II) is trans,trans-hexa-2,4-dien-1-ol or trans-hexa-3-en-1-ol.

7. The method according to any one of claims 1 to 3, 5, wherein the conjugate acid of the base has a pKa of 5 to 14.

8. The method according to any one of claims 1 to 3, 5, wherein the base is a metal phosphate or a metal carbonate.

9. The method according to any one of claims 1 to 3, 5, wherein the base is an alkali metal phosphate, an alkaline earth metal phosphate, an alkali metal carbonate, or an alkaline earth metal carbonate.

10. The aforementioned base is lithium phosphate (Li ３ PO ４ ), sodium phosphate (Na ３ PO ４ ), potassium phosphate (K ３ PO ４ ), or cesium phosphate (Cs ３ PO ４ The method according to any one of claims 1 to 3, 5.

11. The method according to any one of claims 1 to 3, 5, wherein the base exists in a solid form.

12. The method according to any one of claims 1 to 3, 5, wherein the base is present in an amount of 30 to 70 mol% of the total amount of the ester-containing substrate, in an amount of 30 to 60 mol% of the total amount of the ester-containing substrate, or in an amount of 30 to 50 mol% of the total amount of the ester-containing substrate.

13. The method according to claim 1, wherein the transition metal catalyst comprises a tridentate ligand.

14. The transition metal catalyst is a tridentate ligand having formula (III). 【Chemistry 4】 (In the formula, X is -SR ａ , -OR ａ , -CR ａ , -NR ａ R ｂ ,-PR ａ R ｂ , -P(=O)R ａ R ｂ , -OPR ａ R ｂ , and -NHPR ａ R ｂ Selected from; R １ and R ｘ These are, independently, hydrogen, substituted or unsubstituted C １～２０ - Alkyl, substituted, or unsubstituted C ２～２０ - Alkenyl, substituted or unsubstituted C ２～２０ - Alkynyl, substituted or unsubstituted C １～２０ - Heteroalkyl, substituted or unsubstituted C １～２０ - alkoxy, substituted or unsubstituted C ３～２０ - Cycloalkyl, substituted or unsubstituted C ３～２０ - Cycloalkenyl, substituted or unsubstituted C ２～２０ - Heterocycloalkyl, substituted or unsubstituted C ６～２０ - Aryl and substituted or unsubstituted C ４～２０ - Selected from heteroaryls; or R １ and R ３ａ and R ３ｂ One of the two, or R ｘ and R ３ａ and R ３ｂ One of them forms a ring with the atom to which they are bonded; Alternatively, X is a heteroatom, and R ｘ If R does not exist, １ Together with it, it forms a heterocycle that is optionally substituted; Y is -SR ａ , -OR ａ , -CR ａ , -NR ａ R ｂ ,-PR ａ R ｂ , -P(=O)R ａ R ｂ , -OPR ａ R ｂ , and -NHPR ａ R ｂ Selected from; R ２ and R ｙ These are, independently, hydrogen, substituted or unsubstituted C １～２０ - Alkyl, substituted, or unsubstituted C ２～２０ - Alkenyl, substituted or unsubstituted C ２～２０ - Alkynyl, substituted or unsubstituted C １～２０ - Heteroalkyl, substituted or unsubstituted C １～２０ - alkoxy, substituted or unsubstituted C ３～２０ - Cycloalkyl, substituted or unsubstituted C ３～２０ - Cycloalkenyl, substituted or unsubstituted C ２～２０ - Heterocycloalkyl, substituted or unsubstituted C ６～２０ - Aryl and substituted or unsubstituted C ４～２０ - Selected from heteroaryls, or R ２ and R ４ａ and R ４ｂ One of the two, or R ｙ and R ４ａ and R ４ｂ One of them forms a ring with the atom to which they are bonded; Alternatively, Y is a heteroatom, and R ｙ If R does not exist, ２ Together with it, it forms a heterocycle that is optionally substituted; R ３ａ 、 R ３ｂ 、 R ４ａ 、 and R ４ｂ are each independently hydrogen, substituted or unsubstituted C １～２０ -alkyl, substituted or unsubstituted C ２～２０ -alkenyl, substituted or unsubstituted C ２～２０ -alkynyl, substituted or unsubstituted C １～２０ -heteroalkyl, substituted or unsubstituted C １～２０ -alkoxy, substituted or unsubstituted C ３～２０ -cycloalkyl, substituted or unsubstituted C ３～２０ -cycloalkenyl, substituted or unsubstituted C ２～２０ -heterocycloalkyl, substituted or unsubstituted C ６～２０ -aryl, and substituted or unsubstituted C ４～２０ -heteroaryl; or R ３ａ and one of R ４ａ and R ４ｂ forms a heterocycle together with the atom to which they are attached; or R ３ｂ and one of R ４ａ and R ４ｂ forms a heterocycle together with the atom to which they are attached; R ５ C is hydrogen, substituted or unsubstituted. １～２０ - Alkyl, substituted, or unsubstituted C ２～２０ - Alkenyl, substituted or unsubstituted C ２～２０ - Alkynyl, substituted or unsubstituted C １～２０ - Heteroalkyl, substituted or unsubstituted C １～２０ - alkoxy, substituted or unsubstituted C ３～２０ - Cycloalkyl, substituted or unsubstituted C ３～２０ - Cycloalkenyl, substituted or unsubstituted C ２～２０ - Heterocycloalkyl, substituted or unsubstituted C ６～２０ - Aryl and substituted or unsubstituted C ４～２０ - Selected from heteroaryls; Each m and n is independently 1 or 2; and R ａ and R ｂ If present, each independently comprises hydrogen, substituted or unsubstituted C １～２０ - Alkyl, substituted, or unsubstituted C ２～２０ - Alkenyl, substituted or unsubstituted C ２～２０ - Alkynyl, substituted or unsubstituted C １～２０ - Heteroalkyl, substituted or unsubstituted C １～２０ - alkoxy, substituted or unsubstituted C ３～２０ - Cycloalkyl, substituted or unsubstituted C ３～２０ - Cycloalkenyl, substituted or unsubstituted C ２～２０ - Heterocycloalkyl, substituted or unsubstituted C ６～２０ - Aryl and substituted or unsubstituted C ４～２０ - Selected from heteroaryls; or X and / or Y are -NR ａ R ｂ ,-PR ａ R ｂ , -OPR ａ R ｂ or -NHPR ａ R ｂ If R ａ and R ｂ The method according to claim 13, comprising (which together with the heteroatoms to which they are bonded, form a heteroring).

15. The transition metal catalyst is of formula (IV) or formula (V) [M(L) １ )(L ２ ) ｄ ] (UV) [M(L １ )(L ２ ) ｄ ]W (V) (In the formula, M is a transition metal, and the transition metal in the transition metal catalyst is Ru; L １ is a tridentate ligand as defined in claim 14; L ２ These are ligands that may be the same or different; d is 1, 2 or 3; and The method according to any one of claims 1 to 3, 5, wherein W is a non-coordinating anion ligand.

16. Each L ２ However, independently, -H, -CO, -CN, -P(R') ３ , -As(R') ３ , -CR', -OR', -O(C=O)R', -NR' ２ The method according to claim 15, wherein each R' is independently selected from a halogen (e.g., -Cl, -Br, -I) and a solvent, and where R' is independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

17. The transition metal catalyst, 【Transformation 5】 The method according to any one of claims 1 to 3 or 5.

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