Process for selective catalytic hydrogenation of dienones

Abstract

The present disclosure provides a catalyst system capable of selectively hydrogenating (2, 3) / (4, 5) and (2, 3) / (5, 6) dienones with hydrogen. In particular, the present disclosure provides catalysts capable of providing high selectivity for reduction even in the absence of catalyst poisons such as pyridine, pyrazine, quinoline, and quinoxaline.

Description

[0001] The present invention provides a process for the selective hydrogenation of (2,3) / (4,5) unsaturated dienes using rhodium or ruthenium complexes without the need for nitrogen-containing additives such as pyridine, pyrazine, quinoline and quinoxaline. Background Art

[0002] Technical grade pseudoionone (PI) is readily available from vitamin A producers, as it is one of the intermediates of vitamin A (see Tetrahedron 2016, 72, 1645-1652). Direct hydrogenation enables the production of the valuable intermediate geranylacetone from PI. Geranylacetone is classically prepared from linalool as an E / Z-mixture, as described in H.Surburg and J.Panten, Common Fragrance and Flavor Materials, 4th edition, Wiley-VCH, Weinheim 2016. Technical grade PI is produced and used as a mixture of possible stereoisomers in any ratio; i.e., 3E / 5E-PI, 3E / 5Z-PI, 3Z / 5E-PI and 3Z / 5Z-PI. The 3E / 5E-PI isomer is the major isomer of technical grade PI. Geranyl acetone produced from PI by hydrogenation is produced as an E / Z-mixture as shown in Scheme 1 below.

[0003] Solution 1

[0004]

[0005] Processes for the selective monohydrogenation of (2,3) / (4,5)-unsaturated dienes to the corresponding (4,5)-unsaturated enones are known in the literature; however, very few processes are reported to operate with the efficiency required for use in the chemical industry.

[0006] The hydrogenation of β-ionone to the corresponding dihydroionone with a heterogeneous copper catalyst under a hydrogen atmosphere of 1 bar and at 90° C. has been described (Journal of Molecular Catalysis 74, 1992, 267-74). A similar process is described in Catalysts 2020, 10, 515, where the hydrogenation of β-ionone was carried out under 1 bar of hydrogen and at 90° C. Despite these reports, the direct hydrogenation of pseudoionone (PI) to geranylacetone (GAC) with a homogeneous catalyst has only recently been described.

[0007] Compared to β-ionone, pseudoionone (PI) is more challenging as a substrate for selective monohydrogenation at the (2,3)-position because β-ionone is tetrasubstituted at the second double bond, while pseudoionone (PI) is trisubstituted (the substrate-dependent reactivity difference of the two double bonds per molecule is greater for β-ionone than for pseudoionone, which makes the selective monohydrogenation of pseudoionone more difficult). It is further noted in Journal of Molecular Catalysis 74, 1992, 267-74 that for some substrates, such as β-ionone, the yield of the selective monohydrogenation decreases due to isomerization of the second double bond in the molecule. Therefore, heterogeneous catalysts may lead to isomerization of additional double bonds and therefore cannot be used to hydrogenate pseudoionone (PI) to geranylacetone (GAC).

[0008] Organometallics 10, 1982, 1390-1399 reported the use of Et 3 SiH catalyzes the selective reduction of (2,3) / (4,5) unsaturated dienes such as β-ionone to the corresponding dihydroionone. 3 The atom economy of SiH is lower than that of hydrogen.

[0009] CN 105218339 describes the use of Pd(acac) 2 / 1,2-bis(diphenylphosphino)ethane or Rh(PPh 3 ) 3 The conditions for the selective hydrogenation of methylheptyldienone to methylheptanone using Cl / 1,2-bis(diphenylphosphino)ethane as a catalyst.

[0010] WO 2012 / 150053 reports a homogeneous rhodium catalyst system for the selective hydrogenation of (2,3) / (4,5) unsaturated aldehydes to give the corresponding (4,5) unsaturated aldehydes. The patent does not mention the use of such a catalyst system for the selective hydrogenation of (2,3) / (4,5) unsaturated dienes.

[0011] CN 201811560479.9 describes a method for the selective hydrogenation of (2,3) / (4,5) unsaturated diene ketones using Ru complexes in the presence of catalyst poisons. It should be noted that the hydrogenation of pseudoionone (PI) to geranylacetone (GAC) with hydrogen is carried out with high selectivity only in the presence of nitrogen-containing additives such as pyridine, pyrazine, quinoline and quinoxaline.

[0012] Angew Chem. Int. Ed. [Applied Chemistry International Edition], 2019, 58, 12246-51 reported the use of Rh-catalysts to reduce (2,3) / (4,5) unsaturated esters with formic acid (rather than hydrogen) as a reducing agent. However, the atom economy of formic acid is lower than that of hydrogen. In the case disclosed, Z-(3,4) unsaturated esters were obtained.

[0013] Thus, there has been no system described to date which catalyzes the hydrogenation of pseudoionone (PI) to geranylacetone (GAC) with high selectivity using hydrogen in the absence of pyridine, pyrazine, quinoline and quinoxaline. The inventors have surprisingly discovered a catalyst system which is able to hydrogenate PI in the absence of catalyst poisons while maintaining high selectivity. Summary of the invention

[0014] The present disclosure provides a method for the selective hydrogenation of diene ketone. Specifically, the present disclosure provides a method comprising: 1) combining diene ketone with one or more solvents; 2) adding a catalyst to the mixture of diene ketone and solvent to provide a reaction mixture; and 3) reacting the reaction mixture in a gas containing hydrogen (H 2 The catalyst may further comprise one or more ligands, such as monophosphine or diphosphine. The reaction may be carried out in the absence of catalyst poisons such as pyridine, pyrazine, quinoline, or quinoxaline while still maintaining high selectivity. DETAILED DESCRIPTION

[0015] 1. Definition

[0016] In the definitions of the variables given in the above formulae and in the following formulae, collective terms are used which generally represent the corresponding substituents. n - to C m - indicates the corresponding possible number of carbon atoms in a particular substituent or substituent portion.

[0017] In the context of the present invention, the expression "alkyl" includes unbranched or branched alkyl groups having 1 to 4, 6, 12 or 25 carbon atoms. These include, for example, C 1 - to C 6-alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 2-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethylbutyl, 2-ethylbutyl, 1-ethyl-2-methylpropyl, and the like.

[0018] In the context of the present invention, the expression "cycloalkyl" comprises cyclic saturated hydrocarbon groups having 3 to 6, 12 or 25 carbon ring members, for example C 3 -C 8 - cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, or C 7 -C 12 -bicycloalkyl.

[0019] In the context of the present invention, the expression "alkoxy" is an alkyl radical having 1 to 6 carbon atoms bonded via oxygen, for example C 1 - to C 6 -alkoxy, such as methoxy, ethoxy, n-propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy.

[0020] In the context of the present invention, the expression "alkenyl" comprises an unbranched or branched hydrocarbon radical having 2 to 4, 6, 12 or 25 carbon atoms, which comprises at least one double bond, for example 1, 2, 3 or 4 double bonds. These include, for example, C 2 -C 6-alkenyl, such as vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl , 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl.

[0021] In the context of the present invention, the expression "alkylene" refers to a divalent hydrocarbon radical having 2 to 25 carbon atoms. The divalent hydrocarbon radical may be unbranched or branched. These include, for example, C 2 -C 16-alkylene, such as 1,4-butylene, 1,5-pentylene, 2-methyl-1,4-butylene, 1,6-hexylene, 2-methyl-1,5-pentylene, 3-methyl-1,5-pentylene, 1,7-heptylene, 2-methyl-1,6-hexylene, 3-methyl-1,6-hexylene, 2-ethyl-1,5-pentylene, 3-ethyl-1,5-pentylene, 2,3-dimethyl-1,5-pentylene, 2,4-dimethyl-1,5-pentylene, 1,8-octylene, 2-methyl-1,7-heptylene, 3-methyl-1,7-heptylene, 4-methyl-1,7-heptylene, 2-ethyl-1,6-hexylene, 3-ethyl-1,6-hexylene, 2,3-dimethyl-1,6-hexylene, 2,4- dimethyl-1,6-hexylene, 1,9-nonylene, 2-methyl-1,8-octylene, 3-methyl-1,8-octylene, 4-methyl-1,8-octylene, 2-ethyl-1,7-heptylene, 3-ethyl-1,7-heptylene, 1,10-decylene, 2-methyl-1,9-nonylene, 3-methyl-1,9-nonylene, 4-methyl-1,9-nonylene, 5-methyl-1,9-nonylene, 1,11-undecylene, 2-methyl-1,10-decylene, 3-methyl-1,10-decylene, 5-methyl-1,10-decylene, 1,12-dodecylene, 1,13-tridecylene, 1,14-tetradecylene, 1,15-pentadecylene, 1,16-hexadecylene, and the like.

[0022] In singly or multiply branched or substituted alkylene, the carbon atoms at the branch points or the carbon atoms at the corresponding branch points or the carbon atoms carrying substituents may, independently of one another, have the R- or S-configuration or both configurations in equal or different ratios.

[0023] In the context of the present invention, the expression "alkenylene" refers to a divalent hydrocarbon radical having 2 to 25 carbon atoms, which may be unbranched or branched, wherein the main chain has one or more double bonds, for example 1, 2 or 3 double bonds. These include, for example, C 2 - to C 18-alkenylene, such as ethylene, propylene, 1-, 2-butylene, 1-, 2-pentylene, 1-, 2-, 3-hexylene, 1,3-hexadienylene, 1,4-hexadienylene, 1-, 2-, 3-heptylene, 1,3-heptadienylene, 1,4-heptadienylene, 2,4-heptadienylene, 1-, 2-, 3-octenylene, 1,3-octenylene, 1,4-octenylene, 2,4-octenylene, 1-, 2-, 3-nonenylene, 1-, 2-, 3-hexadienylene, 1,3-heptenylene, 1,4-heptenylene, 2,4-heptenylene, 1-, 2-, 3-nonenylene, 1-, 2-, 3 1-, 2-, 3-, 4-, 5-decenylene, 1-, 2-, 3-, 4-, 5-undecenylene, 2-, 3-, 4-, 5-, 6-dodecenylene, 2,4-dodecadienylene, 2,5-dodecadienylene, 2,6-dodecadienylene, 3-, 4-, 5-, 6-tridecenylene, 2,5-tridecadienylene, 4,7-tridecadienylene, 5,8-tridecadienylene, 4-, 5-, 6-, 7-tetradecenylene, 2,5-tetradecadienylene 4,7-pentadecadienylene, 5,8-tetradecadienylene, 4-, 5-, 6-, 7-pentadecadienylene, 2,5-pentadecadienylene, 4,7-pentadecadienylene, 5,8-pentadecadienylene, 1,4,7-pentadecatrienylidene, 4,7,11-pentadecatrienylidene, 4,6,8-pentadecatrienylidene, 4-, 5-, 6-, 7-, 8-hexadecadienylene, 2,5-hexadecadienylene, 4,7-hexadecadienylene yl, 5,8-hexadecadienylene, 2,5,8-hexadecatrienylidene, 4,8,11-hexadecatrienylidene, 5,7,9-hexadecatrienylidene, 5-, 6-, 7-, 8-heptadecadienylene, 2,5-heptadecadienylene, 4,7-heptadecadienylene, 5,8-heptadecadienylene, 5-, 6-, 7-, 8-, 9-octadecadienylene, 2,5-octadecadienylene, 4,7-octadecadienylene, 5,8-octadecadienylene and the like.

[0024] The double bonds in alkenylene can be present independently of one another in the E and also in the Z configuration or as a mixture of the two configurations.

[0025] In the context of the present invention, the expression "halogen" includes fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine or bromine.

[0026] In the context of the present invention, the expression "aryl" comprises mononuclear to trinuclear aromatic ring systems containing 6 to 14 carbon ring members. These include, for example, C 6 - to C 10 - an aryl group, such as phenyl or naphthyl.

[0027] In the context of the present invention, the expression "heteroaryl" comprises mononuclear to trinuclear aromatic ring systems comprising 6 to 14 carbon ring members, wherein one or more (e.g. 1, 2, 3, 4, 5 or 6) carbon atoms are substituted by nitrogen, oxygen and / or sulfur atoms. These include, for example, C 3 - to C 9 - heteroaryl, such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-thiadiazole- 1,2,4-triazine-3-yl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl, etc.

[0028] In the context of the present invention, the expression "aralkyl" comprises mononuclear to dinuclear aromatic ring systems containing 6 to 10 carbon ring members, which are attached via unbranched or branched C 1 - to C 6 -alkyl bonds. These include, for example, C 7 - to C 12 - aralkyl, such as phenylmethyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, etc.

[0029] In the context of the present invention, the expression "aralkyl" comprises mononuclear to dinuclear aromatic ring systems comprising one or more (eg 1, 2 or 3) unbranched or branched C 1 - to C 6 -alkyl-substituted 6 to 10 carbon ring members. These include, for example, C 7 - to C 12- alkylaryl, such as 1-methylphenyl, 2-methylphenyl, 3-methylphenyl, 1-ethylphenyl, 2-ethylphenyl, 3-ethylphenyl, 1-propylphenyl, 2-propylphenyl, 3-propylphenyl, 1-isopropylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 1-butylphenyl, 2-butylphenyl, 3-butylphenyl, 1-isobutylphenyl, 2-isobutylphenyl, 3-isobutylphenyl, 1-sec-butylphenyl, 2-sec-butylphenyl, 3-sec-butylphenyl, 1-tert-butylphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 1-(1-pentenyl)phenyl, 2-(1-pentenyl)phenyl, 3-(1-pentenyl)phenyl, 1-(2-pentenyl)phenyl, 2-(2-pentenyl)phenyl phenyl, 2-(3-pentenyl)phenyl, 3-(3-pentenyl)phenyl, 1-(1-(2-methylbutyl))phenyl, 2-(1-(2-methylbutyl))phenyl, 3-(1-(2-methylbutyl))phenyl, 1-(2-(2-methylbutyl))phenyl, 2-(2-(2-methylbutyl))phenyl, 3-(2-(2-methylbutyl))phenyl, 1-(3-(2-methylbutyl))phenyl, 2-(3-(2-methylbutyl))phenyl, 3-(3-(2-methylbutyl))phenyl, 1-(4-(2-methylbutyl))phenyl, 2-(4-(2-methylbutyl))phenyl, 3-(4-(2-methylbutyl))phenyl 1-(1-(2,2-dimethylpropyl))phenyl, 2-(1-(2,2-dimethylpropyl))phenyl, 3-(1-(2,2-dimethylpropyl))phenyl, 1-(1-hexenyl)phenyl, 2-(1-hexenyl)phenyl, 3-(1-hexenyl)phenyl, 1-(2-hexenyl)phenyl, 2-(2-hexenyl)phenyl, 3-(2-hexenyl)phenyl, 1-(3-hexenyl)phenyl, 2-(3-hexenyl)phenyl, 3-(3-hexenyl)phenyl, 1-(1-(2-methylpentenyl))phenyl, 2-(1-(2-methylpentenyl))phenyl, 3-(1-(2-methylpentenyl))phenyl, 1-(2-(2-methylpentenyl))phenyl, 2 -(2-(2-methylpentenyl))phenyl, 3-(2-(2-methylpentenyl))phenyl, 1-(3-(2-methylpentenyl))phenyl, 2-(3-(2-methylpentenyl))phenyl, 3-(3-(2-methylpentenyl))phenyl, 1-(4-(2-methylpentenyl))phenyl, 2-(4-(2-methylpentenyl))phenyl, 3-(4-(2-methylpentenyl))phenyl, 1-(5-(2-methylpentenyl))phenyl, 2-(5-(2-methylpentenyl))phenyl, 3-(5-(2-methylpentenyl))phenyl, 1-(1-(2,2-dimethylbutenyl))phenyl, 2-(1-(2,2-dimethylbutenyl))phenyl, 3-(1-(2,phenyl, 2-(4-(2,2-dimethylbutenyl))phenyl, 1-(3-(2,2-dimethylbutenyl))phenyl, 2-(3-(2,2-dimethylbutenyl))phenyl, 3-(3-(2,2-dimethylbutenyl))phenyl, 1-(4-(2,2-dimethylbutenyl))phenyl, 2-(4-(2,2-dimethylbutenyl))phenyl, 3-(4-(2,2-dimethylbutenyl))phenyl, etc.

[0030] 2. Catalyst

[0031] The present disclosure provides a catalyst system capable of selectively hydrogenating diene ketones with hydrogen. Suitable diene ketones may include (2,3) / (4,5) and (2,3) / (5,6) diene ketones, such as pseudoionone, β-ionone, 6-methyl-3,5-heptadiene-2-one and α-ionone. Specifically, the present disclosure provides a catalyst capable of providing high selectivity for reduction. Surprisingly, it has been found that the catalyst system of the present disclosure can catalytically hydrogenate under hydrogen in the absence of catalyst poisons such as pyridine, pyrazine, quinoline and quinoxaline while achieving high selectivity. This may be particularly desirable because these catalyst poisons must be removed after the reaction. Therefore, the method of the present disclosure achieves high selectivity, higher atom economy and simpler purification.

[0032] The catalyst may comprise one or more transition metals and one or more ligands.

[0033] The one or more transition metals may be selected from the group comprising ruthenium, rhodium, platinum, palladium and nickel.

[0034] The catalyst can be prepared by reacting a precursor containing a transition metal with a ligand (and possibly an additional reagent such as H 2 , CO, MeOH, reducing agent) in any ratio to form a metal-ligand-complex. For example, when the ligand is a neutral bidentate bisphosphine ligand, the metal-ligand complex can have one of the following forms: (L)M(CO)X; (L)M(CO) 2 X;(L)M(CO)XY;(L)M(CO)XYZ. For example, when the ligand is a monodentate phosphine ligand, the metal-ligand complex can have one of the following forms: (L) 2 M(CO)X;(L) 2 M(CO) 2 X; (L) 3 M(CO)X;(L) 2 M(CO)XY;(L) 2 M(CO)XY;(L) 2M(CO)XYZ. X, Y and Z are each independently an anionic monodentate ligand such as H, Cl, Br, OAc, OH, acac, OMe, OEt or Oalkyl. Suitable metal-containing precursors include Rh(CO) 2 acac, Rh(III) acetate, or [Ru(COD)(2-methylallyl) 2 ].

[0035] Other suitable metal-containing precursors include rhodium or ruthenium metal complexes. Suitable rhodium compounds are in particular those which are soluble in the selected reaction medium, such as, for example, rhodium(0), rhodium(I), rhodium(II) and rhodium(III) salts, such as, for example, rhodium(III) chloride, rhodium(III) bromide, rhodium(III) nitrate, rhodium(III) sulfate, rhodium(II) oxide or rhodium(III) oxide, rhodium(II) acetate or rhodium(III) acetate, rhodium(II) formate or rhodium(III) formate, Rh(acac) 3 , [Rh(cod)Cl] 2 、[Rh(cod) 2 ]BF 4 , Rh 2 (OAc) 4 、bis(ethylene)rhodium(I)acac、Rh(CO) 2 acac, [Rh(cod)OH] 2 , [Rh(cod)OMe] 2 , Rh 4 (CO) 12 or Rh 6 (CO) 16 , where "acac" is the acetylacetonate ligand, "cod" is the cyclooctadiene ligand and "OAc" is the acetate ligand.

[0036] Additional catalyst rhodium compounds may include L 2 Rh(CO)H (where L = monodentate phosphine), L 3 Rh(CO)H (where L = monodentate phosphine) or LRh(CO)H (where L = bidentate phosphine) or LRh(CO) 2 Rhodium compounds containing carbonyl groups of the H type (where L = bidentate phosphine). Such complexes have been used in olefin hydrogenation, for example by Wilkinson et al. in J. Chem. Soc. (A) 1968, 2665-2671 (using (PPh 3 ) 3 Rh(CO)H), or Breit et al. in Tetrahedron Letters 2005, 6171-6179 (using (PPh 3 )3 Rh(CO)H), or by Delongchamps et al. in Can. J. Chem [Canadian Journal of Chemistry] 1990, 2137-2143, or by et al. in Adv.Synth.Catal. 2008, 2708-2714 (using (Chiraphos)Rh(CO) 2 H), but not for the selective hydrogenation of unsaturated dienes. Such carbonyl compounds can be used as isolated complexes or prepared by catalyst preformation.

[0037] For example, suitable ruthenium compounds are in particular those which are soluble in the chosen reaction medium, such as, for example, ruthenium(0), ruthenium(I), ruthenium(II) and ruthenium(III) salts, such as, for example, [Ru(p-cymene)Cl 2 ] 2 、[Ru(CO) 4 (ethylene)], [Ru(COD)(OAc) 2 ]、[Ru(CO) 2 Cl 2 ] n 、[Ru(CO) 3 Cl 2 ] 2 , [RuCl 3 *H 2 O], [Ru(acetylacetonate) 3 ]、[Ru(benzene)Cl 2 ] n 、[Ru(COD)(2-methylallyl) 2 ]、[Ru(DMSO) 4 Cl 2 ]、[Ru(PPh 3 ) 3 (CO)(H)Cl]、[Ru(PPh 3 ) 3 (CO)Cl 2 ]、[Ru(PPh 3 ) 3 (CO)(H) 2 ]、[Ru(PPh 3 ) 3 Cl 2 ]、[Ru(COD)Cl 2 ] 2 , [Ru(pentamethylcyclopentadienyl)(COD)Cl], [Ru 3 (CO) 12 ].

[0038] The ligand may comprise one or more bisphosphines, one or more monophosphines, or a combination thereof. The ligand may be selected from the group consisting of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), bis[(2-diphenylphosphino)phenyl]ether (DPEphos), bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (d ppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), (4,4,4',4',6,6'-hexamethyl-3,3',4,4'-tetrahydro-2,2'-spirobis[[1]benzopyran]-8,8'-diyl)bis(diphenylphosphane) (SPANPhos), triphenyl phosphite (P(OPh) 3 ), 6,6'-[(3,3'-di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(oxy)]bis(6H-dibenzo[d,f][1,3,2]dioxaphosphepine)(BiPhePhos), trimethyl phosphite (P(OMe) 3 ), triethyl phosphite (P(OEt) 3 ), (3,5-dioxa-4-phosphocycloheptyl[2,1-a:3,4-a']dinaphth-4-yl)dimethylamine (MonoPhos), (R,R)Chiraphos, (S,S)Chiraphos, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), triphenylphosphine (PPh 3 ), tris(4-methoxyphenyl)phosphine, tris(3,5-bis(trifluoromethyl)phenyl)phosphine, 1,1'-bis(diisopropylphosphino)ferrocene (dippf) and methyldiphenylphosphine. The structures of the ligands are shown below, where "Me" is understood to mean methyl, "Ph" means phenyl, "Cy" means cyclohexyl, and i Pr means isopropyl alcohol.

[0039]

[0040]

[0041] The transition metal complex can be present in the reaction in an amount of about 0.01 mol % or greater, about 0.05 mol % or greater, about 0.1 mol % or greater, about 0.2 mol % or greater, about 0.3 mol % or greater, about 0.4 mol % or less, about 0.5 mol % or less, about 0.6 mol % or less, about 0.7 mol % or less, about 0.8 mol % or less, about 0.9 mol % or less, about 1.0 mol % or less, or any value included in these endpoints.

[0042] The mol ratio of ligand (which can be a monodentate or bidentate phosphine ligand) to metal can be about 0.9:1 or greater, about 1.0:1 or greater, about 1.5:1 or greater, about 2.0:1 or greater, about 2.5:1 or greater, about 3.0:1 or greater, about 5:1 or greater, about 10:1 or greater, about 20:1 or greater, about 30:1 or greater, about 40:1 or greater, about 50:1 or less, about 60:1 or less, about 70:1 or less, about 80:1 or less, about 90:1 or less, about 100:1 or less or any value comprised by these endpoints. In chemical processes, ligand may be oxidized or partially oxidized over time, for example, by the pollutants in the oxidation feed. In addition, catalyst may be decomposed over time by alkali or thermal stress. Therefore, the optimum ratio of ligand to metal depends on various parameters and can be different in different settings.

[0043] The ligand can be present in the reaction in an amount of about 0.01 mol % or greater, about 0.05 mol % or greater, about 0.1 mol % or greater, about 0.5 mol % or greater, about 1.0 mol % or greater, about 2.0 mol % or greater, about 3.0 mol % or greater, about 4.0 mol % or less, about 5.0 mol % or less, about 6.0 mol % or less, about 7.0 mol % or less, about 8.0 mol % or less, about 9.0 mol % or less, about 10.0 mol % or less, or any value included in these endpoints.

[0044] The reaction can be carried out in a base such as Na 2 CO 3 , NaOMe, NaOEt, or trialkylamines such as, for example, triethylamine, ethyldiisopropylamine and triisopropylamine.

[0045] 3. Reaction conditions

[0046] As shown above, even in the absence of pyridine, pyrazine, quinolone and quinoxaline, the above catalysts can provide high selectivity for the reduction of (2,3) / (4,5) and (2,3) / (5,6) dienones. Suitable dienones may include (2,3) / (4,5) and (2,3) / (5,6) dienones, such as, for example, pseudoionone, β-ionone, 6-methyl-2-hept-5-en-2-one and α-ionone.

[0047] In one embodiment, suitable substrates for the reaction may include (2,3) / (4,5) dienone having Formula I shown below,

[0048]

[0049] Where R 1 It is C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, or with R 2 A bond to form an optionally substituted 5-membered or 6-membered ring; R 2 It is hydrogen, C 1 -C 6 Alkyl, or with R 1 A bond to form an optionally substituted 5-membered or 6-membered ring; R 3 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl; R 4 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 5 forms a bond to an optionally substituted 5-membered or 6-membered ring; and R 5 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 4 A bond to an optionally substituted 5- or 6-membered ring is formed.

[0050] In another embodiment, suitable substrates for the reaction may include a (2,3) / (5,6) dienone having Formula II shown below.

[0051]

[0052] Where R 6 It is C 1 -C 6 Alkyl, or C1 -C 6 Alkoxy; R 7 is hydrogen, or C 1 -C 6 Alkyl; R 8 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl; R 9 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl; R 10 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 11 forms a bond to an optionally substituted 5-membered or 6-membered ring; and R 11 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 10 A bond to an optionally substituted 5- or 6-membered ring is formed.

[0053] To carry out the reaction, the transition metal complex and the ligand can be combined in one or more solvents under an inert atmosphere to provide an active catalyst. For example, the inert atmosphere can include nitrogen (N 2 ) or argon (Ar).

[0054] The molar ratio of transition metal complex to ligand can be 1:1 or greater, 1:1.05 or greater, 1:1.10 or greater, 1:1.20 or greater, 1:1.30 or greater, 1:1.40 or less, 1:1.50 or less, 1:1.60 or less, 1:1.70 or less, 1:1.80 or less, 1:1.90 or less, 1:2.00 or less, 1:2.10 or less, 1:2.20 or less, 1:2.50 or less, 1:3 or less, 1:4 or less, 1:5 or less, or any value included in these endpoints.

[0055] Suitable solvents may include, for example, methanol, ethanol, isopropanol, hexanol, texanol, tetrahydrofuran (THF), toluene, xylene, dioxane, n-butanol, ethyl acetate, dichloromethane (DCM), or diethyl ether (Et 2 O), or a combination thereof.

[0056] The transition metal complex and the ligand can be stirred under an inert atmosphere for a period of about 10 minutes or more, about 20 minutes or more, about 30 minutes or more, about 40 minutes or more, about 50 minutes or more, about 60 minutes or less, about 70 minutes or less, about 80 minutes or less, about 90 minutes or less, or any value included in these endpoints.

[0057] The transition metal complex and the ligand can be preformed by mixing the Rh-precursor and the ligand in any ratio in one or more solvents under an inert atmosphere or under an atmosphere of hydrogen or carbon monoxide or a mixture of hydrogen and carbon monoxide in a pressure range of 1 bar to 100 bar, for example as described in WO 2006 / 40096.

[0058] The transition metal complex and the ligand can be combined at a temperature of about 20°C or more, about 30°C or more, about 40°C or more, about 50°C or less, about 60°C or less, about 70°C or less, about 80°C or less, or any value included by these endpoints.

[0059] The active catalyst can then be combined with a solution comprising a (2,3) / (4,5)dienone. The solution can further comprise an additional solvent, such as, for example, methanol, ethanol, isopropanol, 1-hexanol, 1-decanol, 1-nonanol, texanol (3-hydroxy-2,2,4-trimethylpentyl isobutyrate), tetrahydrofuran (THF), toluene, ethyl acetate, dichloromethane (DCM), MTBE, or diethyl ether (Et 2 O).

[0060] The solution may further comprise one or more cosolvents, such as alkylbenzenes. Suitable alkylbenzenes may include, for example, toluene, ethylbenzene, xylene, mesitylene and durene. Other suitable cosolvents may include, for example, methanol, ethanol, isopropanol, 1-hexanol, 1-decanol, 1-nonanol, texanol (3-hydroxy-2,2,4-trimethylamyl isobutyrate), tetrahydrofuran (THF), dioxane, n-butyl alcohol, ethyl acetate, or diethyl ether (Et 2 (O). As a percentage of the total reaction mass, the co-solvent is most preferably used in an amount of about 5 wt.% or more, about 10 wt.% or more, about 15 wt.% or more, about 20 wt.% or more, about 25 wt.% or more, about 30 wt.% or more, about 40 wt.% or more, about 45 wt.% or less, about 50 wt.% or less, about 55 wt.% or less, about 60 wt.% or less, about 65 wt.% or less, about 70 wt.% or less, about 75 wt.% or less, about 80 wt.% or less, or any value included by these endpoints.

[0061] The amount of (2,3) / (4,5)dienone in the reaction can be about 5% or greater, about 10% or greater, about 15% or greater, about 20% or greater, about 25% or greater, about 30% or greater, about 35% or greater, about 40% or greater, about 45% or greater, about 50% or less, about 55% or less, about 60% or less, about 65% or less, about 70% or less, about 75% or less, about 80% or less, about 85% or less, about 90% or less, about 95% or less, about 99% or less, about 99.9% or less, or any value included in these endpoints. Preferably, the concentration is from about 10% to about 80% as a percentage of the total reaction mixture.

[0062] After adding the active catalyst to the (2,3) / (4,5)dione solution, the (2,3) / (4,5)dione solution can be aerated with hydrogen (H2) to a pressure of 1 to 100 bar. 2 ) instead of nitrogen (N 2 ). The pressure can then be carefully released and the process repeated two more times.

[0063] The reaction can be carried out in hydrogen (H 2 The pressure of the hydrogen atmosphere can be about 1 bar or more, about 5 bar or more, about 10 bar or more, about 20 bar or more, about 30 bar or more, about 40 bar or more, about 50 bar or less, about 60 bar or less, about 70 bar or less, about 80 bar or less, about 90 bar or less, about 100 bar or less, or any value including these endpoints.

[0064] The hydrogen atmosphere may further comprise carbon monoxide (CO). The carbon monoxide may be present in an amount of about 1 ppm or more, about 5 ppm or more, about 10 ppm or more, about 50 ppm or more, about 100 ppm or more, about 200 ppm or more, about 500 ppm or more, about 700 ppm or more, about 1000 ppm or less, about 1200 ppm or less, about 1500 ppm or less, about 1700 ppm or less, about 2000 ppm or less, or any value included in these endpoints.

[0065] The reaction can be carried out at a temperature of about 10°C to about 100°C, e.g., 10°C or more, 20°C or more, about 30°C or more, about 40°C or more, about 50°C or more, about 60°C or less, about 70°C or less, about 80°C or less, about 90°C or less, about or any value included in these endpoints.

[0066] The reaction can be stirred for a period of about 1 hour or more, about 2 hours or more, about 3 hours or more, about 5 hours or more, about 10 hours or more, about 15 hours or more, about 20 hours or more, about 24 hours or more, about 30 hours or less, about 35 hours or less, about 40 hours or less, about 45 hours or less, about 48 hours or less, or any value inclusive of these endpoints.

[0067] The reaction can be carried out batchwise or semicontinuously as well as continuously and is particularly suitable for reactions on an industrial scale.

[0068] The obtained product can be separated from the catalyst by known procedures such as distillation under reduced pressure. The remaining catalyst can be reused.

[0069] Examples

[0070] Unless otherwise stated, all reactions were performed in a N 2 All glassware was dried before use. Pseudoionone (technical grade, isomer mixture, ≥95% (by GC and 1 H NMR))、Ru(COD)(met) 2 and anhydrous methanol were purchased from Sigma-Aldrich. Rh(CO) was synthesized using literature procedures. 2 (acac) (Inorganic Synthesis, 2004, 34, 128). Ligands were purchased from Sigma-Aldrich or Strem Chemicals, Combi-blocks, Alfa Aesar, or Acros (xantphos CAS: 161265-03-8, dpephos CAS: 166330-10-5, dppm CAS: 2071-20-7, dppe CAS: 1663-45-2, dppp CAS: 6737-42-4, dppb CAS: 7688-25-7, dppf CAS: 12150-46-8, binap CAS: 98327-87-8, spanphos CAS: 556797-94-5, P(OPh) 3 CAS: 101-02-0, P(OMe) 3 CAS: 121-45-9, monophos CAS: 252288-04-3, PPh 3 CAS: 603-35-0, P(4-OMeC 6 H 4 ) 3CAS: 855-38-9, P(3,5-CF 3 -C 6 H 3 ) 3 P CAS: 175136-62-6, PPhMe 2 672-66-2, PCy 3 CAS: 2622-14-2, SPhos CAS 657408-07-6, dippf CAS 97239-80-0). Hydrogenations were performed using a Parr high pressure reactor (4750 series vessel with split ring closure). Yields and conversions were determined by gas chromatography using durene as an internal standard using an Agilent J&W HP-5 or DB-5MS column (30 m), unless otherwise stated.

[0071] Example 1: General procedure for the Rh-catalyzed hydrogenation of pseudoionones, 0.2 mmol scale Pseudoionone was reduced according to Scheme 2 below.

[0072] Solution 2

[0073]

[0074] In full N 2 In a glove box, Rh(CO) 2 A stock solution was prepared by mixing (acac) (0.004mmol, 1.0mg) with xantphos (0.0042mmol, 2.4mg) in a 1:1.05 molar ratio in methanol (MeOH) (2mL) for 30min. An aliquot of the catalyst solution (1.0mL, 0.002mmol) was transferred to a vial (1-dram) containing pseudoionone (72%E, 0.2mmol, 38.4mg) and durene (5-10mg) in MeOH (1.0mL). A stirring bar was added to the mixture and the vial was sealed with a PTFE-wire cap. The PTFE-wire cap was pierced with an 18-gauge needle and the vial was then placed in a high pressure reactor. The high pressure reactor was sealed and removed from the glove box. The mixture was heated to 400-800psi with H 2 Replacement reactor N 2 atmosphere, then carefully release the pressure, and repeat the process two more times. 2 Stir under pressure (700-1000 psi). Pressures as low as 100 psi can be used to achieve similar results.

[0075] To determine the crude yield, after the reaction was completed, a small aliquot (about 10 μL) of the reaction mixture was taken out and added to a gas chromatography (GC) vial filled with ethyl acetate (EtOAc), and then analyzed by GC to determine the conversion and yield, which were >99% and 97% (72% E, 28% Z). [GC conditions: HP-5 or DB-5MS, 100°C-300°C, 9 min; retention time on HP-5: pseudoionone: t (3E,5Z) =3.01min, t (3E,5E) =3.24min; Geranyl acetone: t (5Z) =2.57min, t (5E) =2.65min. Retention time on DB-5MS: Pseudoionone: t (3E,5Z) =3.21min, t (3E,5E) =3.46min; Geranyl acetone: t (5Z) =2.74min, t (5E) = 2.830 min. Molar response factors compared to durene internal standard: pseudoionone: 1.1; geranylacetone: 1.2.

[0076] Three other catalysts were used under the same conditions described above. The catalysts and results are shown in Table 1 below.

[0077] Table 1

[0078]

[0079] Example 2: Reduced Catalyst Loading at Higher Temperature

[0080] In this example, pseudoionone (72% E, 0.2 mmol, 38.4 mg) was selectively reduced using the same 0.2 mmol scale general procedure described above. The catalyst was 0.25 mol% Rh(CO) 2 (acac) with 0.53 mol% P(OPh) 3 The reaction was stirred at 50 °C for 24 h.

[0081] The yield was determined as described above, showing a 92% yield and >99% conversion.

[0082] Example 3: Rh-catalyzed hydrogenation of pseudoionone, 1 mmol scale

[0083] In full N 2 In a glove box, Rh(CO) 2(acac) (0.011mmol, 2.8mg) and xantphos (0.012mmol, 6.7mg) were mixed in MeOH (5.5mL) at a 1:1.05 molar ratio for 30min to prepare a stock solution. The catalyst solution (5mL, 0.01mmol) was transferred to a 4-dram vial containing pseudoionone (72%E, 1mmol, 192.3mg) and durene (25mg) in MeOH (5mL). A stirring bar was added to the mixture and the vial was sealed with a PTFE-wire cap. The PTFE-wire cap was pierced with five 18-gauge needles and the vial was then placed in a high pressure reactor. Alternatively, an uncapped 8-dram vial can be used.

[0084] The high pressure reactor was sealed and removed from the glove box. The reactor was then inflated to 600-800 psi with H 2 Replacement reactor N 2 The reaction mixture was stirred under the corresponding H 2 Stir under pressure (1000 psi).

[0085] To determine the crude yield, after the reaction was complete, a small aliquot (approximately 10 μL) of the reaction mixture was removed and added to a GC vial containing EtOAc and then analyzed by GC as described above to determine the conversion and yield, which was >99% and 96% (72% E, 28% Z).

[0086] Example 4: Ligand Screening

[0087] Using the procedure described in Example 1 (yields and conversions determined by GC), Rh(CO) 2 Pseudoionone (72% E, 0.2 mmol, 38.4 mg) was treated with acac (1 mol%) along with various bisphosphines and phosphine ligands. In each case, the reaction was carried out under H 2 The reaction was carried out at 1000 psi at 20 °C at a concentration of 0.1 M in MeOH as shown in Scheme 3.

[0088] Solution 3

[0089]

[0090] The ligands tested and the percent yield and percent conversion are shown below in Table 2. Unless otherwise stated, the ratio of rhodium complex to ligand was 1 :1 for bisphosphines and 1 :2 for monophosphines.

[0091] Table 2

[0092]

[0093]

[0094] *Reaction temperature is 60℃

[0095] Example 5: Reaction Condition Screening

[0096] Using the procedure described in Example 1, as shown in Scheme 4, Rh(CO) 2 Pseudoionone (72% E, 0.2 mmol, 38.4 mg) was treated with acac (1 mol%) and xantphos (1%).

[0097] Solution 4

[0098]

[0099] Various solvents, pressures, temperatures and reaction times were tested. The conditions and results are shown in Table 3 below.

[0100] Table 3

[0101]

[0102] *In this run, no ligand was used. **5:2; HCO 2 H is 2 equivalents Example 6: Catalyst screening

[0103] Using the procedure described in Example 1, pseudoionone (72% E, 0.2 mmol, 38.4 mg) was treated with a 1 mol% amount of the transition metal complex and xantphos (1%) as shown in Scheme 5.

[0104] Solution 5

[0105]

[0106] In each case, the 2 The reaction pressure was 1000 psi under atmosphere; the reaction concentration was 0.1 M (in methanol); and the reaction temperature was 20° C. As shown in Table 4, various transition metal complexes were tested, along with the percent conversion and percent yield.

[0107] Table 4

[0108] experiment Metal complexes % Conversion Rate % Yield 6.1 <![CDATA[[Rh(COD)Cl] 2 ]]> >99 0 6.2 <![CDATA[[Rh(ethylene) 2 Cl] 2 > 91 6 6.3 < 2 ]BF 4 ]]> 54 21 6.4 <![CDATA[RhCl(PPh 3 ) 3 *]]> 0 0 6.5 <![CDATA[Ir(CO) 2 aca**]]> 0 0 6.6 <![CDATA[[Ir(COD)Cl] 2 ]]> 33 9 6.7 <![CDATA[Ru(COD)(methallyl) 2 **]]> >99 23

[0109] *No ligand added**70℃

[0110] Example 7: Ruthenium-catalyzed hydrogenation of pseudoionone

[0111] Solution 6

[0112]

[0113] Ru-catalyzed hydrogenation was performed using the general procedure described in Example 1 (Ru-precursor and ligand substituted for Rh-precursor and ligand). The reaction mixture was heated at 70 °C under H 2 The mixture was stirred at 800 psi under atmosphere. To determine the crude yield, after the reaction was complete, a small aliquot (about 10 μL) of the reaction mixture was removed and added to a GC-vial filled with EtOAc and then analyzed by GC as described above to determine the conversion and yield, (dippf: conversion>99% and yield 92%, 72% E).

[0114] Example 8: Optimization of Ruthenium-Catalyzed Hydrogenation of Pseudoionone

[0115] As shown in Scheme 7, pseudoionone was reacted with H 2 Reduction was performed using ruthenium complexes and various ligands at 800 psi under atmosphere. The reaction concentration was 0.2 M in methanol. The reaction was stirred at 70°C-75°C for 2-3 hours.

[0116] Solution 7

[0117]

[0118] The different ligands along with the percent conversion and percent yield are shown in Table 5 below.

[0119] Table 5

[0120]

[0121]

[0122] As a further variant, two ligands were tested at a reaction time of 1.5 hours. The results of these further tests are shown in Table 6 below.

[0123] Table 6

[0124]

[0125] Example 9.1: Rh(CO) 2 Reactions after pre-formation of acac / xantphos catalyst

[0126] Rh(CO) 2 Acac (43 mg, 0.17 mmol) and xantphos (140 mg, 0.24 mmol) were dissolved in tetrahydrofuran (THF) (27 ml) and heated under syngas (H 2 / CO=1:1, volume / volume) at 1160 psi in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gas dispersion stirrer, 1000 rpm / mm). The reaction was maintained at 70° C. for 16 h, then cooled to 25° C. and the pressure was released. Nitrogen was passed through the solution for two hours. After flushing with nitrogen, pseudoionone (16.2 g, 84.2 mmol) was added to the autoclave via a lock. The reaction pressure was adjusted to 1160 psi with hydrogen and heated to 50° C. The yield and conversion were determined by gas chromatography (RXI-ms column: 20 m×0.18 mm / 0.36 μm; 30 min at 100° C., then 35° C. / h to 300° C.). After a reaction time of 4 hours, a conversion of 97% was observed, and the yield of geranylacetone was 94%.

[0127] Example 9.2: Rh(CO) 2 Reactions after pre-formation of ACAC / DPPE catalyst

[0128] Rh(CO) 2 Acac (43 mg, 0.17 mmol) and dppe (101 mg, 0.25 mmol) were dissolved in texanol (27 ml) and heated under syngas (H 2 / CO=1:1, volume / volume) at 1160 psi in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gas dispersion stirrer, 1000 rpm). The reaction was maintained at 70° C. for 16 h, then cooled to 25° C. and the pressure was released. Nitrogen was passed through the solution for two hours. After flushing with nitrogen, pseudoionone (16.2 g, 84.2 mmol) was added to the autoclave via a lock. The reaction pressure was adjusted to 1160 psi with hydrogen and heated to 50° C. The yield and conversion were determined by gas chromatography (RXI-ms column: 20 m×0.18 mm / 0.36 μm; 30 min at 100° C., then 35° C. / h to 300° C.). After a reaction time of 4 hours, a conversion of> 98% was observed, and the yield of geranylacetone was 97%.

[0129] Example 9.3: Rh(CO) 2 acac / PPh 3 Reactions after catalyst preformation

[0130] Rh(CO) 2 acac (43 mg, 0.17 mmol) and PPh 3 (135 mg, 0.52 mmol) was dissolved in THF (30 ml) and heated under syngas (H 2 / CO=1:1, volume / volume) at 1160 psi in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gas dispersion stirrer, 1000 rpm). The reaction was maintained at 70° C. for 16 h, then cooled to 25° C. and the pressure was released. Nitrogen was passed through the solution for two hours. After flushing with nitrogen, pseudoionone (16.2 g, 84.2 mmol) was added to the autoclave via a lock. The reaction pressure was adjusted to 1160 psi with hydrogen and heated to 50° C. The yield and conversion were determined by gas chromatography (RXI-ms column: 20 m×0.18 mm / 0.36 μm; 30 min at 100° C., then 35° C. / h to 300° C.). After a reaction time of 20 hours, a conversion of> 98% was observed, and the yield of geranylacetone was 97%.

[0131] Example 10: Rh(CO) 2 acac / P(OPh) 3 Reactions after catalyst preformation

[0132] Rh(CO) 2 acac (43 mg, 0.17 mmol) and P(OPh) 3 (155 mg, 0.5 mmol) was dissolved in tetrahydrofuran (THF) (27 ml) and heated to 4 % by sintering under syngas (H 2 / CO=1:1, volume / volume) at 1160psi in a 100ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gas dispersion stirrer, 1000 rpm). The reaction was maintained at 70°C for 16h, then cooled to 25°C and the pressure released. Nitrogen was then passed through the solution for two hours. After flushing with nitrogen, pseudoionone (15.2g, 84.2mmol) was added to the autoclave via a lock. The reaction pressure was adjusted to 1160psi with hydrogen and heated to 50°C. The yield and conversion were determined by gas chromatography. After a reaction time of 20 hours, a conversion of 99% was observed and the yield of geranyl acetone was 91%.

[0133] Example 11: Rh(CO) 2 Scope of acac / xantphos catalytic reduction

[0134] In this example, Rh(CO) 2 Acac / xantphos (L:Rh = 1:1, MeOH, 1 mol% Rh) was used as a catalyst to reduce various substrates. In each case, the reaction was carried out in the presence of H 2 The reaction was carried out under 1000 psi in an atmosphere. The substrates and conditions for each reaction as well as the percent conversion, percent yield and isolated yield are shown in Table 7 below. The reactions were run according to the general procedure described in Example 1, with the variables listed in Table 7, and the isolation schemes for the compounds in Experiments 11.1-11.9 (Compounds 2-9) are shown in the Experimental Data section.

[0135] Table 7

[0136]

[0137]

[0138] *pass 1 Yield and conversion determined by H NMR **nd = not determined

[0139] Example 12: Rh(CO) 2 acac / P(OPh) 3 Scope of catalytic reduction

[0140] In this example, Rh(CO) 2 acac / P(OPh) 3 (L:Rh = 2:1, MeOH, 1 mol% Rh) was used as a catalyst to reduce various substrates. In each case, the reaction was carried out in the presence of H 2 The reaction was carried out under atmosphere at 1000 psi. The substrates and conditions for each reaction as well as the percent conversion and percent yield are shown in Table 8 below. The reactions were run according to the general procedure described in Example 1 with the variables listed in Table 8.

[0141] Table 8

[0142]

[0143] *pass 1 Yield and conversion determined by H NMR

[0144] Experimental data of Examples 3 and 11 and compounds in Table 7

[0145] The results of NMR and high resolution mass spectrometry (HRMS) analyses of the compounds of Examples 3 and 11 are shown below, as well as certain purification conditions.

[0146] Compound 1, Example 3

[0147]

[0148] Compound 1 was prepared from pseudoionone (192.3 mg, 1.0 mmol) according to the procedure described in Example 3. The reaction was carried out to a conversion greater than 98% and a yield of 90% (E / Z ratio of 72:28), as determined by a calibrated GC using durene as an internal standard (ISTD). After purification by flash column chromatography (2% to 18% EtOAc in hexane), the product was isolated as a mixture of geometric isomers (5E:5Z=72:28) as a colorless oil in 88% yield. 1 H NMR (CDCl 3,500MHz)δ5.13-5.04(m,2H),2.44(dt J=7.4,7.1Hz,2H),2.30-2.22(m,2H),2.13(s,3H),2.09-2.01(m,2H),2.00-1.94(m,2H),1.67(s,3H),1.61(s,3H),1.59(s,3H); 13 CNMR (CDCl 3 ,125MHz,main,E-product)δ208.9,136.4,131.5,124.2,122.6,43.8,39.7,30.0,26.7,25.7,22.5,17.7,16.0; 13 C NMR (CDCl 3 , 125MHz, minor, Z-product)δ208.8,136.5,131.7,124.2,123.4,44.1,31.9,29.9,26.5,25.8,23.4,22.3,17.7; HRMS (EI): for C 13 H 22 Calculated value of O [M] + 194.1665. Measured value 194.1672.

[0149] Compound 2, Example 11.7

[0150]

[0151] Compound 2 was prepared from the corresponding diene (29.3 mg, 0.21 mmol) at 50 °C according to the general procedure described in Example 1. 1 The reaction was checked by H NMR to confirm complete consumption of the starting material after 16 hours. The product was isolated as a 75:25 mixture of over-reduced products. 1 H NMR (CDCl 3 ,500MHz)δ5.11-5.06(m,1H),3.67(s,3H),2.36-2.27(m,4H),1.68(s,3H),1.62(s,3H); 13 C NMR (CDCl 3 ,125MHz)δ173.9,133.2,122.4,51.5,34.3,25.7,23.7,17.7;HRMS(EI): for C 8 H 14 O 2 Calculated value of [M] + 142.09938. Found 142.09963. HRMS (EI): for C8 H 14 O 2 Calculated value of [M] + 142.0988. Measured value 142.0996.

[0152] Compound 3, Example 11.4

[0153]

[0154] Compound 3 was prepared from the corresponding diene (18 mg, 0.097 mmol, about 80:20 Z / E) according to the general procedure described in Example 1. The reaction was carried out to a conversion of greater than 98% and a yield of 93% (5Z:5E=83:17), as measured by calibration. 1 H NMR was determined using durene as ISTD.After purification by thin layer chromatography (10% EtOAc in hexanes), the product was isolated in 77% yield (5Z isomer only). 1 H NMR (CDCl 3 ,500MHz)δ7.35-7.31(m,2H),7.24(tt,J=7.4,1.4Hz,1H),7.18-7.15(m,2H),5.41(tq,J=7. 4,1.4Hz,1H),2.43(t,J=7.4Hz,2H),2.25(q,J=7.1Hz,2H),2.07(s,3H),2.02-2.01(m,3H); 13 C NMR (CDCl 3 ,125MHz)δ208.5,141.8,137.7,128.2,127.9,126.7,125.5,44.0,29.8,25.6,23.6;HRMS(EI): for C 13 H 16 Calculated value of O [M] + 188.1196. Measured value 188.1205.

[0155] Compound 4, Example 11.2

[0156]

[0157] Compound 4 was prepared from the corresponding diene (17.8 mg, 0.096 mmol) according to the general procedure described in Example 1. The reaction was carried out to greater than 98% conversion and 95% yield, as measured by calibration. 1 H NMR was determined using durene as ISTD.After purification by thin layer chromatography (10% EtOAc in hexanes), the product was isolated in 85% (5E isomer only).1 H NMR (CDCl 3 ,500MHz)δ7.37-7.34(m,2H),7.32-7.28(m,2H),7.45-7.21(m,1H),5.71(tq,J=7.2,1. 4Hz,1H),2.60,(t,J=7.4Hz,2H),2.48(q,J=7.4Hz,2H),2.17(s,3H),2.06-2.05(m,3H); 13 C NMR (CDCl 3 ,125MHz)δ208.4,143.7,136.0,128.2,126.7,126.4,125.7,43.4,30.0,23.2,15.9;HRMS(EI): for C 13 H 16 Calculated value of O [M] + 188.1196. Measured value 188.1202.

[0158] Compound 5, Example 11.6

[0159]

[0160] Compound 5 was prepared from β-ionone (39.5 mg, 0.21 mmol) at 40°C according to the general procedure described in Example 1. The reaction was carried out to a conversion of greater than 98% by 1 No side products were observed by H NMR. The product was isolated at 99% after purification through a silica plug (25% EtOAc in hexanes). 1 H NMR (CDCl 3 ,500MHz)δ2.52-2.47(m,2H),2.28-2.23(m,2H),2.14(s,3H),1.90(t,J=6.4Hz,2H),1.59-1.53(m,5H),1.43-1.39(m,2H),0.97(s,6H); 13 C NMR (CDCl 3 ,125MHz)δ209.1,136.0,127.8,44.6,39.8,35.1,32.8,29.8,28.5,22.3,19.8,19.5;HRMS(EI): for C 13 H 22 Calculated value of O [M] + 194.1665. Measured value 194.1672.

[0161] Compound 6, Example 11.5

[0162] Compound 6 was prepared from α-ionone (38.5 mg, 0.20 mmol) at 40°C according to the general procedure described in Example 1. The reaction was carried out to a conversion of greater than 98% by 1 No side products were observed by H NMR. The product was isolated at 99% after purification through a silica plug (25% EtOAc in hexanes). 1 H NMR (CDCl 3 ,500MHz)δ5.33(m,1H),2.461(dd,J=12.8,9.9Hz,1H),2.460(d,J=10.2Hz,1H),2. 13(s,3H),1.99-1.94(m,2H),1.76(ddt,J=14.9,10.4,5.6Hz,1H),1.66(dtd,J=2. 1,1.8,0.5Hz,3H),1.60(dddd,J=19.0,9.9,6.7,4.5Hz,1H),1.47(dd,J=4.5,4.5H z,1H),1.40(ddd,J=17.0,9.4,7.7Hz,1H),1.13(m,1H),0.91(s,3H),0.87(s,3H); 13 C NMR (CDCl 3 ,125MHz)δ209.2,135.6,121.1,48.5,43.8,32.6,31.6,30.0,27.7,27.6,24.4,23.6,23.0;HRMS(EI): for C 13 H 22 Calculated value of O [M] + 194.1665. Measured value 194.1670.

[0163] Compound 7, Example 11.3

[0164]

[0165] Compound 7 was prepared according to the general procedure described in Example 1 (0.1 mmol scale procedure) from the corresponding diene (17.2 mg, 0.1 mmol), 0.5 h. 1 H NMR Diene conversion: >98%, crude yield: 84%. Isolated by silica column chromatography (10% EtOAc in hexanes) in 83% yield. 1 H NMR (CDCl 3,700MHz)δ7.33-7.28(m,4H),7.21-7.19(m,1H),6.41(d,J=15.6Hz,1H),6.20( dt,J=16.0,7.0Hz,1H),2.61(t,J=7.6Hz,2H),2.51-2.49(m,2H),2.17(s,3H); 13 C NMR (CDCl 3 ,125MHz)δ208.1,137.5,130.8,128.9,128.6,127.2,126.1,43.3,30.1,27.2;HRMS(EI): for C 12 H 14 Calculated value of O [M] + 174.1039. Measured value 174.1044.

[0166] Compound 9, Example 11.9

[0167]

[0168] Compound 9 was prepared according to the general procedure described in Example 1 (0.1 mmol scale procedure) from the corresponding diene (23.4 mg, 0.1 mmol), 4h. 1 H NMR Diene conversion: 85%, crude yield: 84%. Isolated by silica column chromatography (2% EtOAc in hexanes) in 84% yield. 1 H NMR (CDCl 3 ,500MHz)δ8.00-7.97(m,2H),7.59-7.55(m,1H),7.50-7.45(m,2H),7.36-7.32(m,2H),7.31-7.27(m,2H),7.2 2-7.18(m,1H),6.47(d,J=15.8Hz,1H),6.30(dt,J=15.7,6.8Hz,1H),3.16(t,J=7.6Hz,2H),2.69-2.64(m,2H); 13 C NMR (CDCl 3 ,125MHz)δ199.4,137.5,136.9,133.1,130.9,129.2,128.7,128.6,128.1,127.1,126.1,38.3,27.6;HRMS(EI): for C 17 H 16 Calculated value of O [M] + 236.1196. Measured value 236.1199.

[0169] Comparative Example A:

[0170] Finally, previously known conditions were tested using pseudoionone as a substrate, as shown in Scheme 8 below.

[0171] Solution 8

[0172]

[0173] The reaction mixture was analyzed at two different time periods and the results are shown in Table 9 below.

[0174] Table 9

[0175] experiment time product(%) SM (% conversion) Z:E 13.1 1h 0 0 --- 13.2 17h 15 24 25:75

[0176] It can be seen that in the case of pseudoionones, previously known conditions failed to provide acceptable conversions and selectivities.

[0177] Example

[0178] Embodiment 1 is a method for selectively hydrogenating a diene ketone, the method comprising: 1) combining a diene ketone with one or more solvents; 2) adding a catalyst to the mixture of the diene ketone and the solvent to provide a reaction mixture; 3) reacting the reaction mixture with a gas containing hydrogen (H 2 ) atmosphere; wherein the catalyst comprises one or more transition metals and one or more ligands; and wherein the reaction is carried out in the absence of pyridine, pyrazine, quinoline and quinoxaline.

[0179] Embodiment 2 is the method of embodiment 1, wherein the one or more transition metals are selected from the group consisting of ruthenium, rhodium, platinum, palladium and nickel.

[0180] Embodiment 3 is the method of embodiment 1 or embodiment 2, wherein the one or more transition metals include rhodium or ruthenium metal complexes.

[0181] Embodiment 4 is the method of any one of embodiments 1 to 3, wherein the one or more transition metals include Rh(CO) 2 acac, Rh(III) acetate, or [Ru(COD)(2-methylallyl) 2 ].

[0182] Embodiment 5 is the method of embodiment 4, wherein the one or more transition metals include Rh(CO 2 )acac.

[0183] Embodiment 6 is the method of embodiment 4, wherein the one or more transition metals include [Ru(COD)(2-methylallyl) 2 ].

[0184] Embodiment 7 is a method as described in any one of embodiments 1 to 6, wherein the one or more ligands are selected from the group consisting of: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), bis[(2-diphenylphosphino)phenyl]ether (DPEphos), bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1, 4-Bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), (4,4,4',4',6,6'-hexamethyl-3,3',4,4'-tetrahydro-2,2'-spirobis[[1]benzopyran]-8,8'-diyl)bis(diphenylphosphane) (SPANPhos), triphenyl phosphite (P(OPh) 3 ), trimethyl phosphite (P(OMe) 3 ), triethyl phosphite (P(OEt) 3 ), (3,5-dioxa-4-phospho[2,1-a:3,4-a']dinaphth-4-yl)dimethylamine (MonoPhos), 6,6'-[(3,3'-di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(oxy)]bis(6H-dibenzo[d,f][1,3,2]dioxaphosphine) (BiPhePhos), (R,R)Chiraphos, (S,S)Chiraphos, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), triphenylphosphine (PPh 3 ), tris(4-methoxyphenyl)phosphine, tris(3,5-bis(trifluoromethyl)phenyl)phosphine, 1,1'-bis(diisopropylphosphino)ferrocene (dippf), and methyldiphenylphosphine.

[0185] Embodiment 8 is a method as described in any one of embodiments 1 to 7, wherein the one or more ligands are selected from the group comprising: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), 1,2-bis(diphenylphosphino)ethane (dppe), (3,5-dioxa-4-phosphocycloheptyl[2,1-a:3,4-a']dinaphth-4-yl)dimethylamine (MonoPhos), (R,R)Chiraphos, (S,S)Chiraphos and triphenyl phosphite.

[0186] Embodiment 9 is the method of any one of embodiments 1 to 7, wherein the one or more ligands are selected from the group consisting of 1,1'-bis(diisopropylphosphino)ferrocene (dippf) and 1,4-bis(diphenylphosphino)butane (dppb).

[0187] Embodiment 10 is the method of any one of embodiments 1 to 9, wherein the one or more ligands are combined with the transition metal or transition metal complex in a molar ratio of about 1:1 to about 10:1.

[0188] Embodiment 11 is the method of any one of embodiments 1 to 10, wherein the transition metal complex is present in the reaction in an amount of about 0.01 mol % to about 1.0 mol %.

[0189] Embodiment 12 is the method of any one of embodiments 1 to 11, wherein the ligand is present in the reaction in an amount of about 0.01 mol % to about 10.0 mol %.

[0190] Embodiment 13 is the method of any one of embodiments 1 to 12, wherein the one or more solvents are selected from the group consisting of methanol, 1-butanol, 1-propanol, 2-propanol, tetrahydrofuran, toluene, ethyl acetate, and ethanol.

[0191] Embodiment 14 is the method of any one of embodiments 1 to 13, further comprising one or more co-solvents.

[0192] Embodiment 15 is the method of embodiment 14, wherein the co-solvent comprises alkylbenzene.

[0193] Embodiment 16 is the method of any one of embodiments 1 to 15, wherein the hydrogen atmosphere is at a pressure of about 1 bar to 100 bar, preferably 5 bar to 90 bar, more preferably 10 bar to 80 bar.

[0194] Embodiment 17 is the method of embodiment 16, wherein the hydrogen atmosphere further comprises carbon monoxide in an amount of about 1 ppm to about 2000 ppm.

[0195] Embodiment 18 is the method of any one of embodiments 1 to 17, wherein the diene ketone is a (2,3) / (4,5) unsaturated diene ketone having formula I

[0196]

[0197] Where R 1 It is C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, or with R 2A bond to form an optionally substituted 5-membered or 6-membered ring; R 2 It is hydrogen, C 1 -C 6 Alkyl, or with R 1 A bond to form an optionally substituted 5-membered or 6-membered ring; R 3 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl; R 4 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 5 forms a bond to an optionally substituted 5-membered or 6-membered ring; and R 5 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 4 A bond to an optionally substituted 5- or 6-membered ring is formed.

[0198] Embodiment 19 is the method as described in embodiment 18, wherein R 1 It is C 1 -C 6 Alkyl or C 1 -C 6 Alkoxy; R 2 is hydrogen or C 1 -C 6 Alkyl; R 3 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl; and R 4 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl.

[0199] Embodiment 20 is the method as described in embodiment 18, wherein R 1 It is C 1 -C 6 Alkyl; R 2 is hydrogen; R 3 It is C 1 -C 6 alkyl; and R 4 It is C 1 -C 10 Alkenyl.

[0200] Embodiment 21 is the method of embodiment 18, wherein the (2,3) / (4,5) unsaturated diene ketone comprises β-ionone or pseudoionone.

[0201] Embodiment 22 is the method of any one of embodiments 1 to 17, wherein the diene ketone is a (2,3) / (5,6) unsaturated diene ketone having Formula II shown below,

[0202]

[0203] Where R 6 It is C 1 -C 6 Alkyl, or C 1 -C 6 Alkoxy; R 7 is hydrogen, or C 1 -C 6 Alkyl; R 8 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl; R 9 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 alkenyl, or aryl; R 10 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 11 forms a bond to an optionally substituted 5-membered or 6-membered ring; and R 11 It is hydrogen, C 1 -C 6 Alkyl, C 1 -C 10 Alkenyl, aryl, or R 10 A bond to an optionally substituted 5- or 6-membered ring is formed.

[0204] Embodiment 23 is the method of embodiment 22, wherein the (2,3) / (5,6) unsaturated diene ketone comprises α-ionone.

[0205] Embodiment 24 is the method of any one of embodiments 1 to 23, wherein the diene ketone is monohydrogenated.

[0206] Embodiment 25 is the method of any one of embodiments 1 to 24, wherein the active catalyst comprises Rh(CO) 2 acac or Ru(COD)met 2and one or more of the following: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), bis[(2-diphenylphosphino)phenyl]ether (DPEphos), bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), (4,4,4',4',6,6'-hexamethyl-3,3',4,4'-tetrahydro-2,2'-spirobis[[1]benzopyran]-8,8'-diyl)bis(diphenylphosphine) (SPANPhos), triphenyl phosphite (P(OPh) 3 ), trimethyl phosphite (P(OMe) 3 ), (3,5-dioxa-4-phospho[2,1-a:3,4-a']dinaphth-4-yl)dimethylamine (MonoPhos), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), triphenylphosphine (PPh 3 ), tris(4-methoxyphenyl)phosphine, tris(3,5-bis(trifluoromethyl)phenyl)phosphine, 1,1'-bis(diisopropylphosphino)ferrocene (dippf), and methyldiphenylphosphine.

[0207] Embodiment 26 is the method of any one of embodiments 1 to 25, wherein the reaction is carried out substantially in the absence of pyridine, pyrazine, quinoline and quinoxaline.

[0208] Embodiment 27 is a method as described in any one of embodiments 1 to 26, wherein the catalyst is preformed by mixing the Rh-precursor and the ligand in a solvent in any ratio under an inert atmosphere or under an atmosphere of hydrogen or carbon monoxide or a mixture of hydrogen and carbon monoxide in a pressure range of 1 bar to 100 bar.

[0209] Embodiment 28 is the method of any one of embodiments 1 to 27, wherein the catalyst is L 2 Rh(CO)H or L 3 Rh-phosphine catalysts containing a carbonyl group of the type Rh(CO)H, in which L is a monodentate phosphine or a monodentate phosphite.

[0210] Embodiment 29 is the method of any one of embodiments 1 to 27, wherein the catalyst is L'Rh(CO) or L'Rh(CO) 2 H-type Rh-phosphine catalysts containing carbonyl groups, in which L' is a bidentate phosphine or bidentate phosphite).

Claims

1. A process for the selective monohydrogenation of diene ketones with hydrogen, the process comprising: 1) combining the diene ketone with one or more solvents or without a solvent; 2) adding a catalyst to a mixture of diene ketone and a solvent or to pure diene ketone to provide a reaction mixture; 3) contacting the reaction mixture with an atmosphere comprising hydrogen (H2); wherein the catalyst comprises a transition metal and one or more phosphine ligands and / or one or more neutral and / or anionic ligands; and The reaction is carried out in the absence of pyridine, pyrazine, quinoline and quinoxaline.

2. The method of claim 1, wherein: The transition metal is selected from the group consisting of ruthenium, rhodium, platinum, palladium and nickel.

3. The method according to claim 1 or 2, wherein: The catalyst comprises a rhodium or ruthenium metal complex.

4. The method according to any one of claims 1 to 3, wherein: The catalyst is formed by reacting a transition metal-containing precursor with the ligand to form a transition metal-ligand complex, wherein the metal-containing precursor comprises Rh(CO)2acac, Rh(III) acetate, or [Ru(COD)(2-methylallyl)2].

5. The method of claim 4, wherein: The transition metal containing precursor is Rh(CO)2acac.

6. The method of claim 4, wherein: The transition metal containing precursor is [Ru(COD)(2-methylallyl)2].

7. The method according to any one of claims 1 to 6, wherein: The one or more ligands are selected from the group consisting of CO, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), bis[(2-diphenylphosphino)phenyl]ether (DPEphos), bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (d ppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), (4,4,4',4',6,6'-hexamethyl-3,3',4,4'-tetrahydro-2,2'-spirobis[[1]benzopyran]-8,8'-diyl)bis(diphenylphosphane) (SPANPhos), triphenyl phosphite (P(OPh)3), triphenylphosphite methyl ester (P(OMe)3), triethyl phosphite (P(OEt)3), (3,5-dioxa-4-phosphocyclohepta[2,1-a:3,4-a']dinaphth-4-yl)dimethylamine (MonoPhos), 6,6'-[(3,3'-di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(oxy)]bis(6H-dibenzo[d,f][1,3,2]di oxaphosphine) (BiPhePhos), (R,R)Chiraphos, (S,S)Chiraphos, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphine, tris(3,5-bis(trifluoromethyl)phenyl)phosphine, 1,1'-bis(diisopropylphosphino)ferrocene (dippf) and methyldiphenylphosphine.

8. The method according to any one of claims 1 to 7, wherein: The one or more ligands are selected from the group including: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), 1,2-bis(diphenylphosphino)ethane (dppe), 1,4-bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf), (3,5-dioxa-4-phosphocycloheptyl[2,1-a:3,4-a']dinaphth-4-yl)dimethylamine (MonoPhos), (R,R)Chiraphos, (S,S)Chiraphos and triphenyl phosphite, triphenylphosphine (PPh3).

9. The method according to any one of claims 1 to 7, wherein: The one or more ligands are selected from the group consisting of 1,1'-bis(diisopropylphosphino)ferrocene (dippf) and 1,4-bis(diphenylphosphino)butane (dppb).

10. The method according to any one of claims 1 to 9, wherein: The one or more ligands are combined with the transition metal or transition metal complex in a molar ratio of about 1:1 to about 10:

1.

11. The method according to any one of claims 1 to 10, wherein: The transition metal complex is present in the reaction in an amount of about 0.01 mol % to about 1.0 mol %.

12. The method according to any one of claims 1 to 11, wherein: The ligand is present in the reaction in an amount of about 0.01 mol % to about 10.0 mol %.

13. The method according to any one of claims 1 to 12, wherein: The one or more solvents are selected from the group consisting of methanol, 1-butanol, 1-propanol, 2-propanol, 1-hexanol, 1-decanol, 1-nonanol, texanol (3-hydroxy-2,2,4-trimethylpentyl isobutyrate), tetrahydrofuran, 2-methyl-tetrahydrofuran, MTBE, toluene, ethyl acetate and ethanol.

14. The method according to any one of claims 1 to 13, wherein: The one or more solvents are selected from the group consisting of methanol, 1-butanol, 1-propanol, 2-propanol, tetrahydrofuran, toluene, ethyl acetate and ethanol.

15. The method of any one of claims 1 to 14, further comprising one or more co-solvents.

16. The method of claim 15, wherein: The co-solvent includes an alkylbenzene.

17. The method according to any one of claims 1 to 16, wherein: The hydrogen atmosphere is at a pressure of about 1 bar to 100 bar, preferably 5 bar to 90 bar, more preferably 10 bar to 80 bar.

18. The method according to any one of claims 1 to 17, wherein: The reaction is carried out at a temperature of about 10°C to about 100°C, preferably 10°C to 90°C, more preferably 20°C to 80°C, particularly preferably 30°C to 70°C.

19. The method of claim 17, wherein: The hydrogen atmosphere further comprises carbon monoxide in an amount ranging from about 1 ppm to about 2000 ppm.

20. The method of any one of claims 1 to 18, wherein: The diene ketone is a (2,3) / (4,5) unsaturated diene ketone having the formula I Where R 1 is C1-C6 alkyl, C1-C6 alkoxy, or 2 a bond to form an optionally substituted 5- or 6-membered ring; R 2 is hydrogen, C1-C6 alkyl, or R 1 a bond to form an optionally substituted 5- or 6-membered ring; R 3 is hydrogen, C1-C6 alkyl, C1-C 10 alkenyl, or aryl; R 4 is hydrogen, C1-C6 alkyl, C1-C 10 Alkenyl, aryl, or R 5 A bond to form an optionally substituted 5-membered or 6-membered ring; and R 5 is hydrogen, C1-C6 alkyl, C1-C 10 Alkenyl, aryl, or R 4 A bond to an optionally substituted 5- or 6-membered ring is formed.

21. The method of claim 19, wherein: R 1 is C1-C6 alkyl or C1-C6 alkoxy; R 2 is hydrogen or C1-C6 alkyl, R 3 is hydrogen, C1-C6 alkyl, C1-C 10 alkenyl, or aryl; and R 4 is hydrogen, C1-C6 alkyl, C1-C 10 alkenyl, or aryl.

22. The method of claim 19, wherein: R 1 is a C1-C6 alkyl group; R 2 It is hydrogen; R 3 is a C1-C6 alkyl group; and R 4 It is C1-C 10 Alkenyl.

23. The method of claim 19, wherein: The (2,3) / (4,5) unsaturated dienone comprises β-ionone, 6-methyl-3,5-heptadien-2-one or pseudoionone.

24. The method of any one of claims 1 to 18, wherein: The diene ketone is a (2,3) / (5,6) unsaturated diene ketone having the formula II shown below, Where R 6 is a C1-C6 alkyl group or a C1-C6 alkoxy group; R 7 is hydrogen, or C1-C6 alkyl; R 8 is hydrogen, C1-C6 alkyl, C1-C 10 alkenyl, or aryl; R 9 is hydrogen, C1-C6 alkyl, C1-C 10 alkenyl, or aryl; R 10 is hydrogen, C1-C6 alkyl, C1-C 10 Alkenyl, aryl, or R 11 A bond to form an optionally substituted 5-membered or 6-membered ring; and R 11 is hydrogen, C1-C6 alkyl, C1-C 10 Alkenyl, aryl, or R 10 A bond to an optionally substituted 5- or 6-membered ring is formed.

25. The method of claim 23, wherein: The (2,3) / (5,6) unsaturated diene ketone comprises an α-ionone.

26. The method of any one of claims 1 to 24, wherein: The active catalyst comprises Rh(CO)2acac or Ru(COD)met2 and one or more of the following: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), bis[(2-diphenylphosphino)phenyl]ether (DPEphos), bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), (4,4,4',4',6,6'-hexa Methyl-3,3',4,4'-tetrahydro-2,2'-spirobis[[1]benzopyran]-8,8'-diyl)bis(diphenylphosphane) (SPANPhos), triphenyl phosphite (P(OPh)3), trimethyl phosphite (P(OMe)3), (3,5-dioxa-4-phosphocyclohepta[2,1-a:3,4-a']dinaphth-4-yl)dimethylamine (MonoPhos), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphane, tris(3,5-bis(trifluoromethyl)phenyl)phosphane, 1,1'-bis(diisopropylphosphino)ferrocene (dippf) and methyldiphenylphosphane.

27. The method of any one of claims 1 to 25, wherein: The reaction proceeds substantially in the absence of pyridine, pyrazine, quinoline and quinoxaline.

28. The method of any one of claims 1 to 26, wherein: The catalyst is preformed by mixing the Rh-precursor and the ligand in any ratio in a solvent under an inert atmosphere or under an atmosphere of hydrogen or carbon monoxide or a mixture of hydrogen and carbon monoxide in a pressure range of 1 bar to 100 bar.

29. The method of any one of claims 1 to 27, wherein: The catalyst comprises a transition metal, a phosphine ligand and a carbonyl ligand.

30. The method of any one of claims 1 to 28, wherein: The catalyst is a carbonyl-containing Rh-phosphine catalyst of the type L2Rh(CO)H or L3Rh(CO)H, wherein L is a monodentate phosphine or a monodentate phosphite.

31. The method of any one of claims 1 to 28, wherein: The catalyst is a carbonyl-containing Rh-phosphine catalyst of the type L'Rh(CO) or L'Rh(CO)2H, wherein L' is a bidentate phosphine or bidentate phosphite).

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