Improved enantioselective hydrogenation of 4-substituted 1,2-dihydroquinolines in the presence of chiral iridium catalysts and additives

Abstract

The present invention relates to a process for preparing optically active 4-substituted 1,2,3,4-tetrahydroquinolines, which comprises the enantioselective hydrogenation of the corresponding 4-substituted 1,2-dihydroquinolines in the presence of a chiral iridium (P,N)-ligand catalyst and an additive.

Description

[Technical field]

[0001] The present invention relates to a process for preparing optically active 4-substituted 1,2,3,4-tetrahydroquinolines, comprising the enantioselective hydrogenation of the corresponding 4-substituted 1,2-dihydroquinolines in the presence of a chiral iridium (P,N)-ligand catalyst and an additive. [Background technology]

[0002] It is known from EP 0 654 464 that N-acetyl-tetrahydroquinolines can be converted into the corresponding 4-aminoindan derivatives via a rearrangement reaction.

[0003] 4-Aminoindan derivatives are important intermediates for the preparation of various N-indanylheteroarylcarboxamides with fungicidal activity (EP 0 654 464, WO 2011 / 162397, WO 2012 / 084812, WO 2015 / 197530).

[0004] EP 3 103 789 discloses a method for the optical resolution of 1,1,3-trimethyl-4-aminoindan by converting the enantiomeric mixture into the diastereomeric salts of D-tartaric acid. (R)- and (S)-1,1,3-trimethyl-4-aminoindan are obtained after separation and basification of the diastereomeric salts. This reference also discloses a method for racemizing the undesired enantiomer, so that the overall method allows the undesired enantiomer to be converted into the desired enantiomer via several process steps. (R)-1,1,3-trimethyl-4-aminoindan is a key intermediate for the preparation of the pyrazole carboxamide fungicide impirfluxam.

[0005] Methods for preparing chiral intermediates of N-indanylheteroarylcarboxamides by asymmetric synthesis are also known. WO 2015 / 141564 describes a method for preparing optically active 4-substituted 1,2,3,4-tetrahydroquinolines, which involves hydrogenation of the corresponding 4-substituted 1,2-dihydroquinolines in the presence of a transition metal catalyst bearing a photoactive ligand. Asymmetric hydrogenation of 4-substituted NH-dihydroquinolines proceeded with moderate conversions (up to 62.6%) and enantioselectivities (up to 71.3% ee), whereas N-acetyl-dihydroquinolines gave poorer conversions (up to 14%) and enantioselectivities (up to 31% ee). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] EP 0 654 464 [Patent Document 2] EP 0 654 464 [Patent Document 3] WO 2011 / 162397 [Patent Document 4] WO 2012 / 084812 [Patent Document 5] WO 2015 / 197530 [Patent Document 6] EP 3 103 789 [Patent Document 7] WO 2015 / 141564 Summary of the Invention

[0007] In view of the above prior art, it is an object of the present invention to provide a method for preparing optically active 4-substituted 1,2,3,4-tetrahydroquinolines that has advantages over the prior art methods. This method should allow the preparation of the desired enantiomer in high yield and high enantiomeric purity with few process steps and few purification steps.

[0008] The above object is achieved by the method of the present invention, [ka] [During the ceremony, R 1 is C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy-C1-C6-alkyl, C3-C6-cycloalkyl, C6-C 14 -Aryl, or C6-C 14 -aryl-C1-C4-alkyl, wherein the C1-C6-alkyl, C3-C6-cycloalkyl and C1-C6-alkoxy in the C1-C6-alkoxy-C1-C6-alkyl moiety may be optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy and phenyl, wherein the phenyl may be optionally substituted by 1 to 5 substituents independently selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, and Here, the C6-C 14 -Aryl and C6-C 14 -Aryl-C1-C4-alkyl moiety C6-C 14 -aryl is each unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, R 2 and R 3 are identical and selected from the group consisting of hydrogen, C1-C6-alkyl, C1-C6-haloalkyl and C1-C6-alkoxy-C1-C6-alkyl, or R 2 and R 3 together with the carbons to which they are attached form a C3-C6-cycloalkyl ring, R 4is hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylamino, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl, C2-C6-alkenyloxy, 9-fluorenylmethyleneoxy, C6-C 14 -Aryl, C6-C 14 -Aryloxy, C6-C 14 -aryl-C1-C4-alkyloxy or C6-C 14 -aryl-C1-C4-alkyl, Here, the C6-C 14 -aryl, by itself or as part of a compound substituent, is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy; n is 0, 1, 2, 3 or 4; Each substituent R 5 are, if present, independently selected from the group consisting of halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, hydroxyl, amino and -C(=O)-C1-C6-alkyl. A method for preparing a compound of the formula: In the presence of a chiral iridium catalyst, and In the presence of additives Formula (II) [ka] [In the formula, substituent R 1 , R 2 , R 3 , R 4 , R 5 and the integer n is as defined for compounds of formula (Ia) or (Ib). The method includes the enantioselective hydrogenation of a compound of the formula: The chiral iridium catalyst is represented by formula (IIIa), (IIIb), (IVa), (IVb), (IXa) or (IXb): [ka] [During the ceremony, R 6 , R 7 and R 8 are, independently of one another, hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C4-alkyl, C6-C 14 -Aryl and C6-C 14 -aryl-C1-C4-alkyl, wherein the C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C7-cycloalkyl and C3-C7-cycloalkyl in the C3-C7-cycloalkyl-C1-C4-alkyl moiety are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-haloalkyl and C1-C4-haloalkoxy, and Here, the C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl is optionally substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and phenyl, where the phenyl is also unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 9 and R 10 are, independently of one another, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, di(C1-C6-alkyl)amino, C3-C 12-Cycloalkyl, C3-C 12 -Cycloalkyl-C1-C4-alkyl, C6-C 14 -Aryl, C6-C 14 -aryloxy and C6-C 14 -aryl-C1-C4-alkyl, wherein said C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy and di(C1-C6-alkyl)amino are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy and phenyl, wherein said phenyl is optionally substituted by 1 to 5 substituents independently selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, Here, the C6-C 14 -Aryl, C6-C 14 -aryloxy and C3-C 12 -cycloalkyl, in each case by itself or as part of a composite substituent, may be optionally substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and phenyl, where the phenyl is unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, or R 9 and R 10 together with the phosphorus atom to which they are attached form a phosphorane ring, which may be substituted by one or two C1-C6-alkyl groups, or R 9 and R 10 Together, [ka] wherein the bonds identified by "x" and "y" are both attached directly to the phosphorus atom; p and q are independently selected from 0, 1 and 2; R 11 and R 12 are independently selected from C1-C6-alkyl and phenyl, which may be substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-alkoxy and phenyl, which may be substituted by 1 or 2 C1-C4-alkyl substituents, m is 1 or 2; A is, [ka] where the bond identified with an "*" is attached directly to the phosphorus atom and the bond identified with a "#" is attached directly to the oxazoline moiety; R 13 is C1-C6-alkyl, C1-C6-haloalkyl, C3-C 12 -Cycloalkyl, C3-C 12 -Cycloalkyl-C1-C4-alkyl, C1-C4-alkyl-C3-C7-cycloalkyl, C6-C 14 -Aryl or C6-C 14 -aryl-C1-C4-alkyl, Here, the C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl, in each case, is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C-C-alkyl, C-C-haloalkyl, C-C-alkoxy and C-C-haloalkoxy; R 14 and R 15 are each independently hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C 12-Cycloalkyl, C3-C7-cycloalkyl-C1-C4-alkyl, C1-C4-alkyl-C3-C7-cycloalkyl, C6-C 14 -Aryl and C6-C 14 -aryl-C1-C4-alkyl, Here, the C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl, in each case, is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, R 14 and R 15 together with the carbons to which they are attached form a C5-C6-cycloalkyl ring, R 16 and R 17 are, independently of one another, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, di(C1-C6-alkyl)amino, C3-C 12 -Cycloalkyl, C3-C 12 -Cycloalkyl-C1-C4-alkyl, C6-C 14 -Aryl, C6-C 14 -aryloxy and C6-C 14 -aryl-C1-C4-alkyl, wherein said C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-cycloalkyl and di(C1-C6-alkyl)amino are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy and phenyl, wherein said phenyl is optionally substituted by 1 to 5 substituents independently selected from halogen, C1-C4-alkyl, phenyl, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, and Here, the C6-C 14 -Aryl, C6-C 14 -C6-C in aryl-C1-C4-alkyl 14 -Aryl, C6-C 14 -aryloxy and C3-C 12 -cycloalkyl, in each case by itself or as part of a compound substituent, may be optionally substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, phenyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, or R 16 and R 17 together with the phosphorus atom to which they are attached form a phospholane ring, which may be substituted by one or two C1-C6-alkyl groups, or R 16 and R 17 Together, [ka] wherein the bonds identified by "x" and "y" are both attached directly to the phosphorus atom; p and q are independently selected from 0, 1 and 2; and R 11 and R 12are independently selected from C1-C6-alkyl and phenyl, which may be substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-alkoxy and phenyl, which may be substituted by 1 or 2 C1-C4-alkyl substituents, R 19 is independently selected from phenyl, benzyl, t-butyl, isopropyl, and cyclohexyl; R 20 are independently selected from hydrogen, methyl, ethyl, and isopropyl; R 21 are independently selected from hydrogen, benzyl, methyl, and ethyl; R 22 are independently selected from cyclohexyl, phenyl, 2-methylphenyl, 4-methylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, and 2,4,6-trimethylphenyl. The chiral ligand of The additive achieved in the above method is selected from the group consisting of Bronsted acids, Lewis acids, and mixtures thereof.

[0009] Surprisingly, it has been found that optically active 4-substituted 1,2,3,4-tetrahydroquinolines (Ia and Ib) can be prepared in high yields and with excellent enantioselectivities by enantioselective hydrogenation of the corresponding 4-substituted 1,2-dihydroquinolines (II) in the presence of a chiral iridium (P,N)-ligand catalyst and an additive.

[0010] definition In the definitions of the symbols given in the formula above, collective terms have been used which generally represent the following substituents:

[0011] halogen: Fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine, and more preferably fluorine or chlorine.

[0012] Alkyl:Saturated, linear or branched hydrocarbyl substituents having 1 to 6, preferably 1 to 4, carbon atoms, such as (but not limited to) C1-C6-alkyl groups, such as methyl, ethyl, propyl (n-propyl), 1-methylethyl (iso-propyl), butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylbutyl (tert-butyl), phenyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl. , 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl. In particular, said groups are C1-C4-alkyl groups, such as methyl, ethyl, propyl, 1-methylethyl (isopropyl), butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl) or 1,1-dimethylethyl (tert-butyl) groups. This definition, unless otherwise defined, also includes alkyl as part of a complex substituent, such as C3-C6-cycloalkyl-C1-C4-alkyl, C6 ... 14 -aryl-C1-C4-alkyl, etc.

[0013] Alkenyl:Unsaturated, linear or branched hydrocarbyl substituents having 2 to 6, preferably 2 to 4, carbon atoms and one double bond at any position, such as (but not limited to) C2-C6-alkenyl, such as vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, isopropenyl, homoallyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, 2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, (E )-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl, (Z)-1- Methylbut-2-enyl, (E)-3-methylbut-1-enyl, (Z)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (Z)-2-methylbut-1-enyl, (E)-1-methylbut-1-enyl, (Z)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl, (E)-3,3-dimethylprop-1-enyl, (Z)-3,3-dimethylprop-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z) -Hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, 4-methylpent-4-enyl, 3-methylpent-4-enyl, 2-methylpent-4-enyl, 1-methylpent-4-enyl, 4-methylpent-3-enyl, (E)-3-methylpent-3-enyl, (Z)-3-methylpent-3-enyl, (E)-2-methylpent-3-enyl, (Z)-2-methylpent-3-enyl,(E)-1-methylpent-3-enyl, (Z)-1-methylpent-3-enyl, (E)-4-methylpent-2-enyl, (Z)-4-methylpent-2-enyl, (E)-3-methylpent-2-enyl, (Z)-3-methylpent-2-enyl, (E)-2-methylpent-2-enyl, (Z)-2-methylpent-2-enyl, (E)-1-methylpent-2-enyl, (Z)-1-methylpent-2-enyl, (E)-4-methylpent-1-enyl, (Z)-4-methylpenta -1-enyl, (E)-3-methylpent-1-enyl, (Z)-3-methylpent-1-enyl, (E)-2-methylpent-1-enyl, (Z)-2-methylpent-1-enyl, (E)-1-methylpent-1-enyl, (Z)-1-methylpent-1-enyl, 3-ethylbut-3-enyl, 2-ethylbut-3-enyl, 1-ethylbut-3-enyl, (E)-3-ethylbut-2-enyl, (Z)-3-ethylbut-2-enyl, (E)-2-ethylbut-2-enyl, (Z)- 2-Ethylbut-2-enyl, (E)-1-ethylbut-2-enyl, (Z)-1-ethylbut-2-enyl, (E)-3-ethylbut-1-enyl, (Z)-3-ethylbut-1-enyl, 2-ethylbut-1-enyl, (E)-1-ethylbut-1-enyl, (Z)-1-ethylbut-1-enyl, 2-propylprop-2-enyl, 1-propylprop-2-enyl, 2-isopropylprop-2-enyl, 1-isopropylprop-2-enyl, (E)-2-propylprop-1-enyl nyl, (Z)-2-propylprop-1-enyl, (E)-1-propylprop-1-enyl, (Z)-1-propylprop-1-enyl, (E)-2-isopropylprop-1-enyl, (Z)-2-isopropylprop-1-enyl, (E)-1-isopropylprop-1-enyl, (Z)-1-isopropylprop-1-enyl, 1-(1,1-dimethylethyl)ethenyl, buta-1,3-dienyl, penta-1,4-dienyl, hexa-1,5-dienyl or methylhexadienyl. In particular, said groups are vinyl or allyl. This definition also applies to alkenyl as part of a compound substituent, unless otherwise defined.

[0014] Alkynyl:Linear or branched hydrocarbyl substituents having 2 to 8, preferably 2 to 6, more preferably 2 to 4 carbon atoms and one triple bond at any position, such as (but are not limited to) C2-C6-alkynyl, such as ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, 1-methylprop-2-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, hex-1-ynyl, hex-2-ynyl, hex- 3-ynyl, hex-4-ynyl, hex-5-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl, 1,1-dimethylbut-2-ynyl, or 3,3-dimethylbut-1-ynyl group. In particular, said alkynyl group is ethynyl, prop-1-ynyl, or prop-2-ynyl. This definition also applies to alkynyl as part of a compound substituent, unless otherwise defined.

[0015] Alkylamino:Monoalkylamino or dialkylamino, where monoalkylamino represents an amino group having one alkyl residue with 1-4 carbon atoms attached to the nitrogen atom. Non-limiting examples include methylamino, ethylamino, n-propylamino, iso-propylamino, n-butylamino, and tert-butylamino. Wherein dialkylamino represents an amino group having two independently selected alkyl residues, each having 1-4 carbon atoms attached to the nitrogen atom. Non-limiting examples include N,N-dimethylamino, N,N-diethylamino, N,N-diisopropylamino, N-ethyl-N-methylamino, N-methyl-Nn-propylamino, N-iso-propyl-Nn-propylamino, and N-tert-butyl-N-methylamino.

[0016] Alkoxy: Saturated, linear or branched alkoxy substituents having 1 to 6, more preferably 1 to 4, carbon atoms, such as (but not limited to) C1-C6-alkoxy, such as methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, 1,1-dimethylpropoxy, oxy, 1,2-dimethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-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 and 1-ethyl-2-methylpropoxy. This definition also applies to alkoxy as part of a compound substituent, unless otherwise defined.

[0017] Cycloalkyl:Monocyclic or polycyclic saturated hydrocarbyl substituents having 3 to 12, preferably 3 to 8 and more preferably 3 to 6 carbon ring members, such as (but not limited to) cyclopropyl, cyclopentyl, cyclohexyl and adamantyl. This definition also applies to cycloalkyl, such as C3-C6-cycloalkyl-C1-C4-alkyl, as part of a compound substituent, unless otherwise defined.

[0018] Haloalkyl : linear or branched alkyl substituents having 1 to 6, preferably 1 to 4, carbon atoms (as specified above), in which some or all of the hydrogen atoms in these groups are replaced by halogen atoms as defined above, such as (but not limited to) C1-C3-haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and 1,1,1-trifluoroprop-2-yl. This definition also applies to haloalkyl as part of a compound substituent, unless otherwise defined.

[0019] Haloalkenyl and haloalkynyl are defined similarly to haloalkyl, except that instead of an alkyl group, an alkenyl and alkynyl group are present as part of the substituent.

[0020] Haloalkoxy:Straight or branched alkoxy substituents (as specified above) having 1 to 6, preferably 1 to 4, carbon atoms in which some or all of the hydrogen atoms are replaced by halogen atoms as defined above, such as (but not limited to) C1-C3-haloalkoxy, such as chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and 1,1,1-trifluoroprop-2-oxy. pentafluoroethoxy and 1,1-trifluoroprop-2-oxy. This definition also applies to haloalkoxy as part of a compound substituent, unless otherwise defined.

[0021] Aryl: Monocyclic, bicyclic or tricyclic aromatic or partially aromatic substituents having 6 to 14 carbon atoms, such as (but not limited to) phenyl, naphthyl, tetrahydronaphthyl, indenyl and indanyl. The bond to the superordinate general structure can be via any available ring member of the aryl residue. Aryl is preferably selected from phenyl, 1-naphthyl, 2-naphthyl, 9-phenanthryl and 9-anthracenyl. Phenyl is particularly preferred.

[0022] The term "enantioselective" as used herein means that one of the two possible enantiomers of the hydrogenation product, i.e., the enantiomer of formula (Ia) or the enantiomer of formula (Ib), is preferentially formed. "Enantiomeric excess" or "ee" indicates the degree of enantioselectivity:

[0023]

number

[0024] The major enantiomer can be controlled by the choice of chiral ligand, for example by choosing a chiral ligand of formula (IIIa) or the opposite enantiomer (a ligand of formula (IIIb)), or by choosing a chiral ligand of formula (IVa) or the opposite enantiomer (a ligand of formula (IVb)), respectively.

[0025] The process according to the invention is used to prepare compounds of formula (Ia) or (Ib), preferably (Ia).

[0026] Preferred are compounds of formula (Ia) or (Ib), especially compounds of (Ia), in which the substituents are defined as follows: R 1 is C1-C6-alkyl or C6-C 14 -aryl-C1-C4-alkyl, Here, C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, R 2 and R 3 are identical and selected from C1-C4-alkyl, R 4 is C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenyl or benzyl, n is 0, 1, or 2; Each substituent R 5 If present, is independently selected from the group consisting of halogen, C1-C6-alkyl and C1-C6-haloalkyl.

[0027] More preferred are compounds of formula (Ia) or (Ib), especially compounds of (Ia), wherein the substituents are defined as follows: R 1 is C1-C6-alkyl, R 2 and R 3 are identical and selected from C1-C4-alkyl, R 4 is C1-C4-alkyl, C1-C4-haloalkyl, phenyl or benzyl, n is 0, 1 or 2; Each substituent R 5 When present, is independently selected from the group consisting of halogen and C1-C6-alkyl.

[0028] Even more preferred are compounds of formula (Ia) or (Ib), in particular compounds of (Ia), in which the substituents are defined as follows: R 1 is methyl, ethyl or n-propyl, R 2 and R 3 is methyl, R 4 is C1-C4-alkyl, n is 0, 1 or 2; Each substituent R 5 When present, is independently selected from the group consisting of halogen and C1-C6-alkyl.

[0029] Most preferred are compounds of formula (Ia) or (Ib), especially compounds of (Ia), wherein the substituents are defined as follows: R 1 is methyl or n-propyl, R 2 and R 3 is methyl, R 4 is methyl, n is 0 or 1, Substituent R5 When present, it is fluorine.

[0030] The process according to the invention comprises the enantioselective hydrogenation of a compound of formula (II). 1 , R 2 , R 3 , R 4 , R 5 and the integer n is as defined for compounds of formula (Ia) or (Ib), respectively.

[0031] The enantioselective hydrogenation of the compound of formula (II) is carried out in the presence of an additive selected from the group consisting of Bronsted acids, Lewis acids, and mixtures thereof.

[0032] In a preferred embodiment of the method according to the invention, the additive is selected from the group consisting of hexafluorophosphoric acid, acetic acid, trifluoromethylsulfonic acid, water, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, tetrafluoroboric acid, tetrafluoroboric acid diethyl ether complex, Nafion, Amberlyst, 1,1,1,3,3,3-hexafluoromethyl-2-(trifluoromethyl)propan-2-ol, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, borane tetrahydrofuran complex, boric acid, aluminum(III) trifluoromethanesulfonate, zinc(II) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, complexes of boron trifluoride and mixtures thereof.

[0033] Suitable complexes of boron trifluoride are complexes of boron trifluoride with organic solvents, such as dialkyl ethers or alcohols, and complexes of boron trifluoride with organic acids, such as carboxylic acids. Preferred boron trifluoride complexes are selected from the group consisting of boron trifluoride-diethyl ether complex, boron trifluoride acetate complex, and boron trifluoride n-propanol complex.

[0034] In a more preferred embodiment of the method according to the invention, the additive is selected from the group consisting of hexafluorophosphoric acid, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, tetrafluoroborate diethyl ether complex, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof, wherein the boron trifluoride complex is preferably selected from the group consisting of boron trifluoride-diethyl ether complex, boron trifluoride acetate complex and boron trifluoride n-propanol complex.

[0035] In an even more preferred embodiment of the method according to the invention, the additive is selected from the group consisting of hexafluorophosphoric acid, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof, the boron trifluoride complexes being preferably selected from the group consisting of boron trifluoride diethyl ether complex, boron trifluoride acetate complex and boron trifluoride n-propanol complex.

[0036] In the most preferred embodiment of the method according to the invention, the additive is selected from the group consisting of aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, tris(2,3,4,5,6-pentafluorophenyl)borane, hexafluorophosphoric acid, boron trifluoride, boron trifluoride-diethyl ether complex, boron trifluoride acetate complex and boron trifluoride n-propanol complex.

[0037] The amount of the additive selected from the group consisting of Bronsted acids and Lewis acids used is preferably in the range of 0.1 mol % to 10 mol %, more preferably 0.2 mol % to 5 mol %, most preferably 0.3 mol % to 2 mol %, in particular 0.4 mol % to 1 mol %, based on the amount of the compound of formula (II).

[0038] The enantioselective hydrogenation of a compound of formula (II) is carried out in the presence of a chiral iridium catalyst comprising a chiral ligand of formula (IIIa), (IIIb), (IVa) or (IVb).

[0039] In a preferred embodiment of the process according to the invention, the substituents of formulae (Ia), (Ib), (II), (IIIa), (IIIb), (IVa), (IVb), (IXa) and (IXb) are defined as follows: R 1 is C1-C6-alkyl or C6-C 14 -aryl-C1-C4-alkyl, Here, C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, R 2 and R 3 are identical and selected from C1-C4-alkyl, R 4 is C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenyl or benzyl, n is 0, 1 or 2; Each substituent R 5 is, if present, independently selected from the group consisting of halogen, C-C-alkyl and C-C-haloalkyl; R 6 is C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl or C6-C 14 -aryl, Here, the C6-C 14 -aryl is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and phenyl, where the phenyl is also unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 7 and R 8 are each independently hydrogen, C1-C6-alkyl, C6-C 14 - selected from the group consisting of aryl, C1-C6-alkoxy or C1-C6-haloalkyl, Here, the C6-C 14 -aryl is unsubstituted or substituted by 1 to 5 C1-C4-alkyl substituents, R 9 and R 10 are independently C1-C6-alkyl, C1-C6-alkoxy, di(C1-C6-alkyl)amino, C3-C 12 -Cycloalkyl, C6-C 14 -Aryl, C6-C 14 -aryloxy and C6-C 14 -aryl-C1-C4-alkyl, wherein the C1-C6-alkyl, C1-C6-alkoxy and di(C1-C6-alkyl)amino moieties are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy and phenyl, wherein the phenyl is optionally substituted by 1 to 5 substituents independently selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, Here, the C6-C 14 -Aryl, C6-C 14 -aryloxy and C3-C 12 -cycloalkyl, by itself or as part of a composite substituent, is in each case unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and phenyl, where the phenyl is unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 9 and R 10 together with the phosphorus atom to which they are attached form a phospholane ring, which may be substituted by one or two C1-C6-alkyl groups, m is 1 or 2; A is, [ka] wherein the bond identified with an "*" is attached directly to the phosphorus atom and the bond identified with a "#" is attached directly to the oxazoline moiety; R 13 is C3-C6-alkyl, C3-C 12 -Cycloalkyl, C6-C 14 -Aryl or C6-C 14 -aryl-C1-C4-alkyl, Here, the C6-C 14 -Aryl and C6-C14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl, in each case, is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C-C-alkyl, C-C-haloalkyl, C-C-alkoxy and C-C-haloalkoxy; R 14 and R 15 are, independently of each other, C1-C6-alkyl, C3-C 12 -Cycloalkyl, C6-C 14 -Aryl and C6-C 14 -aryl-C1-C4-alkyl, Here, the C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, or R 14 and R 15 together with the carbons to which they are attached form a C5-C6-cycloalkyl ring, R 16 and R 17 are, independently of each other, C1-C6-alkyl, C3-C 12 -Cycloalkyl, C6-C 14 -Aryl and C6-C 14 -aryl-C1-C4-alkyl, wherein the C1-C6-alkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy and phenyl, wherein the phenyl is optionally substituted by 1 to 5 substituents independently selected from halogen, C1-C4-alkyl, phenyl, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, and Here, the C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl, in each case, is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, R 16 and R 17 together with the phosphorus atom to which they are attached form a phospholane ring, which may be substituted by one or two C1-C6-alkyl groups, R 19 is phenyl, t-butyl, R 20 is hydrogen, methyl, R 21 is benzyl, methyl, R 22 is cyclohexyl, The additives are hexafluorophosphoric acid, trifluoromethylsulfonic acid, water, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, tetrafluoroboric acid, tetrafluoroboric acid diethyl ether complex, Nafion, Amberlyst, 1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, and borane tetrahydrofuran complex. boric acid, aluminum(III) trifluoromethanesulfonate, zinc(II) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, boron trifluoride complexes and mixtures thereof, wherein said boron trifluoride complexes are preferably selected from the group consisting of boron trifluoride-diethyl ether complex, boron trifluoride acetate complex and boron trifluoride n-propanol complex.

[0040] In a more preferred embodiment of the process according to the invention, the substituents of formulae (Ia), (Ib), (II), (IIIa), (IIIb), (IVa), (IVb), (IXa) and (IXb) are defined as follows: R 1 is C1-C6-alkyl, R 2 and R 3 are identical and selected from C1-C4-alkyl, R 4 is C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenyl or benzyl, n is 0, 1 or 2; Each substituent R 5 is, if present, independently selected from the group consisting of halogen, C-C-alkyl and C-C-haloalkyl; R 6is selected from the group consisting of 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl or phenyl, which are unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-alkyl, C1-C4-haloalkyl and phenyl, where the phenyl is also unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 7 and R 8 are, independently of one another, hydrogen or C1-C6-alkyl, R 9 and R 10 are independently selected from the group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl; m is 1 or 2; A is, [ka] wherein the bond identified with an "*" is attached directly to the phosphorus atom and the bond identified with a "#" is attached directly to the oxazoline moiety; R 13 is tert-butyl, iso-propyl or phenyl, R 14 and R 15 is methyl, R 16 and R 17 are each the same and are 2-methylphenyl or 3,5-bismethylphenyl, and the additive is selected from the group consisting of aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, tris(2,3,4,5,6-pentafluorophenyl)borane, hexafluorophosphoric acid, boron trifluoride, and a complex of boron trifluoride, wherein the complex of boron trifluoride is preferably selected from boron trifluoride-diethyl ether complex, boron trifluoride acetate complex, and boron trifluoride n-propanol complex; R 19 is phenyl, R 20 is methyl, R 21 is benzyl, R 22 is cyclohexyl, and the additive is selected from the group consisting of hexafluorophosphoric acid, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,5,4,6-pentafluorophenyl)borane, aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof, wherein the complexes of boron trifluoride are preferably selected from boron trifluoride-diethyl ether complex, boron trifluoride acetate complex, and boron trifluoride n-propanol complex.

[0041] In the most preferred embodiment of the process according to the invention, the substituents of formulae (Ia), (Ib), (II), (IIIa) and (IIIb) are defined as follows: R 1 is C1-C4-alkyl, R 2 and R 3 is methyl, R 4 is C1-C4-alkyl, n is 0 or 1, R 5 is fluorine, if present; R 6is phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl or 2,6-diethyl-4-methylphenyl, R 7 is hydrogen, R 8 is hydrogen or methyl, R 9 and R 10 are each the same and are selected from the group consisting of ethyl, iso-propyl, tert-butyl, cyclopentyl, adamantyl, and cyclohexyl; m is 1.

[0042] In a preferred embodiment of the process according to the invention, a ligand of formula (IIIa) or (IIIb) is used. Depending on whether compound (Ia) or (Ib) is the desired product, the ligand of formula (IIIa) or (IIIb) is selected.

[0043] Preferred are ligands of formula (IIIa) and (IIIb), in which the substituents are defined as follows: R 6 is C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl or C6-C 14 -aryl, Here, the C6-C 14 -aryl is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and phenyl, where the phenyl is also unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 7 and R8 are independently hydrogen, C1-C6-alkyl, C1-C6-alkoxy, C6-C 14 -aryl or C1-C6-haloalkyl, Here, the C6-C 14 -aryl is unsubstituted or substituted by 1 to 5 C1-C4-alkyl substituents, R 9 and R 10 are independently C1-C6-alkyl, C1-C6-alkoxy, di(C1-C6-alkyl)amino, C3-C 12 -Cycloalkyl, C6-C 14 -Aryl, C6-C 14 -aryloxy and C6-C 14 -aryl-C1-C4-alkyl, wherein the C1-C6-alkyl, C1-C6-alkoxy and di(C1-C6-alkyl)amino moieties are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy and phenyl, wherein the phenyl is optionally substituted by 1 to 5 substituents independently selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, and Here, the C6-C 14 -Aryloxy, C3-C 12 -Cycloalkyl and C6-C 14 - aryl, by itself or as part of a composite substituent, in each case unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and phenyl, where the phenyl is unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 9 and R 10together with the phosphorus atom to which they are attached form a phosphorane ring, which may be substituted by one or two C1-C6-alkyl groups, and m is 1 or 2.

[0044] More preferred are ligands of formula (IIIa) and (IIIb), where the substituents are defined as follows: R 6 is selected from the group consisting of 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl or phenyl, which is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-alkyl, C1-C4-haloalkyl and phenyl, where the phenyl is also unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 7 and R 8 are, independently of one another, hydrogen or C1-C6-alkyl, R 9 and R 10 are independently selected from the group consisting of ethyl, isopropyl, sec-butyl, isobutyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl, and m is 1 or 2.

[0045] Most preferred are ligands of formula (IIIa) and (IIIb), where the substituents are defined as follows: R 6 is selected from the group consisting of phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl or 2,6-diethyl-4-methylphenyl, R 7 is hydrogen, R 8 is hydrogen or methyl, R 9 and R 10 are each the same and are tert-butyl, cyclopentyl, or cyclohexyl; and m is 1.

[0046] In another preferred embodiment of the process according to the invention, a ligand of formula (IVa) or (IVb) is used. Depending on whether compound (Ia) or (Ib) is the desired product, the ligand of formula (IVa) or (IVb) is selected.

[0047] Preferred are ligands of formula (IVa) and (IVb), in which the substituents are defined as follows: A is, [ka] wherein the bond identified with an "*" is attached directly to the phosphorus atom and the bond identified with a "#" is attached directly to the oxazoline moiety; R 13 is C3-C6-alkyl, C3-C 12 -Cycloalkyl, C6-C 14 -Aryl or C6-C 14 -aryl-C1-C4-alkyl, Here, the C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl, in each case, is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C-C-alkyl, C-C-haloalkyl, C-C-alkoxy and C-C-haloalkoxy; R 14 and R 15 are, independently of each other, C1-C6-alkyl, C6-C 14-Aryl, C3-C 12 -Cycloalkyl, and C6-C 14 -aryl-C1-C4-alkyl, Here, C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, or R 14 and R 15 together with the carbons to which they are attached form a C5-C6-cycloalkyl ring, R 16 and R 17 are, independently of each other, C1-C6-alkyl, C3-C 12 -Cycloalkyl, C6-C 14 -Aryl and C6-C 14 -aryl-C1-C4-alkyl, wherein the C1-C6-alkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy and phenyl, wherein the phenyl is optionally substituted by 1 to 5 substituents independently selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, and Here, the C6-C 14 -Aryl and C6-C 14 -C6-C in aryl-C1-C4-alkyl moieties 14 -aryl, in each case, is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl, phenyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, or R16 and R 17 together with the phosphorus atom to which they are attached form a phospholane ring, which may be substituted by one or two C1-C6-alkyl groups.

[0048] More preferred are ligands of formula (IVa) and (IVb), in which the substituents are defined as follows: A is, [ka] wherein the bond identified with an "*" is attached directly to the phosphorus atom and the bond identified with a "#" is attached directly to the oxazoline moiety; R 13 is iso-propyl, sec-butyl, iso-butyl, tert-butyl, phenyl or benzyl, R 14 and R 15 are independently selected from the group consisting of C1-C6-alkyl and C6-aryl-C1-C4-alkyl, Here, C6-C 14 -C6-aryl in the aryl-C1-C4-alkyl moiety is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen and C1-C4-alkyl, R 16 and R 17 are, independently of each other, phenyl, 1-naphthyl or 2-naphthyl, They are in each case unsubstituted or substituted by 1 to 5 C1-C4-alkyl substituents.

[0049] Most preferred are ligands of formula (IVa) and (IVb), where the substituents are defined as follows: A is, [ka] where the bond identified with an "*" is attached directly to the phosphorus atom and the bond identified with a "#" is attached directly to the oxazoline moiety, R 13 is tert-butyl, R 14 and R 15 is methyl, and R 16 and R 17 are, independently of one another, phenyl, which is substituted by one or two methyls, in particular R 16 and R 17 are each the same and are phenyl, which is substituted by one or two methyls, or R 16 and R 17 are the same and are 2-methylphenyl or 3,5-dimethylphenyl.

[0050] In another preferred embodiment of the process according to the invention, a ligand of formula (IXa) or (IXb) is used. Depending on whether compound (Ia) or (Ib) is the desired product, the ligand of formula (IXa) or (IXb) is selected.

[0051] Preferred are ligands of formula (IXa) and (IXb), in which the substituents are defined as follows: R 19 is independently selected from phenyl, benzyl, t-butyl, isopropyl, and cyclohexyl; R 20 are independently selected from hydrogen, methyl, ethyl, and isopropyl; R 21 is independently selected from hydrogen, benzyl, methyl, ethyl, and R 22 are independently selected from cyclohexyl, phenyl, 2-methylphenyl, 4-methylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, and 2,4,6-trimethylphenyl.

[0052] More preferred are ligands of formula (IXa) and (IXb), in which the substituents are defined as follows: R 19 is phenyl, t-butyl, R 20 is hydrogen, methyl, R 21 is benzyl, methyl, and R 22 is cyclohexyl.

[0053] Most preferred are ligands of formula (IXa) and (IXb), where the substituents are defined as follows: R 19 is phenyl, R 20 is methyl, R 21 is benzyl, and R 22 is cyclohexyl.

[0054] Preferably, the chiral iridium catalyst is selected from the group consisting of [IrL*(COD)]Y and [IrL*(nbd)]Y, wherein L* is a chiral ligand of formula (IIIa), (IIIb), (IVa) or (IVb), COD stands for 1,5-cyclooctadiene nbd represents norbornadiene, and Y is [B(R 18 )4] - , PF6 - , SbF6 - , CF3SO3 - , [Al{OC(CF3)3}4]- (Formula (VII)) and Δ-TRISPHAT (Formula (VIII)). [ka] [In the formula, R 18is selected from fluorine and phenyl, which is unsubstituted or substituted by 1 to 5 substituents selected from C1-C4-alkyl, C1-C4-haloalkyl and halogen.

[0055] More preferred are chiral iridium catalysts of formula [IrL*(COD)]Y and [IrL*(nbd)]Y, where Y is PF6, [Al{OC(CF3)3}4]- (formula (VII)) or [B(R 18 )4] - and R 18 is phenyl, which is unsubstituted or substituted with 1 to 5 substituents selected from fluorine and trifluoromethyl.

[0056] Even more preferred are compounds of the general formulae (Va), (Vb), (VIa) and (VIb) [ka] [During the ceremony, R 6 is selected from the group consisting of 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl, or phenyl; wherein 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl and phenyl are unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-alkyl, C1-C4-haloalkyl and phenyl, wherein the phenyl is also unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 7 and R 8 are, independently of one another, hydrogen, C1-C6-alkyl or C1-C6-alkoxy, R 9 and R 10are each independently selected from the group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl; m is 1 or 2; R 13 is iso-propyl, sec-butyl, iso-butyl, tert-butyl, phenyl or benzyl, R 14 and R 15 are independently selected from the group consisting of C1-C6-alkyl and C6-aryl-C1-C4-alkyl, Here, the C6-C 14 -C6-aryl in the aryl-C1-C4-alkyl moiety is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen and C1-C4-alkyl, R 16 and R 17 are, independently of each other, phenyl, 1-naphthyl or 2-naphthyl, They are, in each case, unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-haloalkyl, and R 18 is phenyl, which is unsubstituted or substituted by 1 to 5 substituents selected from fluorine and C1-C4-haloalkyl; is a chiral iridium catalyst.

[0057] Particularly preferred are chiral iridium catalysts of general formulae (Va), (Vb), (VIa) and (VIb), in which R 6is selected from the group consisting of phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl and 2,6-diethyl-4-methylphenyl; R 7 is hydrogen, R 8 is hydrogen or methyl, R 9 and R 10 are each the same and are tert-butyl, adamantyl, cyclopentyl, or cyclohexyl; m is 1, R 13 is tert-butyl, R 14 and R 15 is methyl, R 16 and R 17 are, independently of one another, phenyl, which is substituted by one or two methyls, in particular R 16 and R 17 are each the same and are 2-methylphenyl or 3,5-dimethylphenyl, and R 18 is 3,5-bis(trifluoromethyl)phenyl.

[0058] Most preferred are chiral iridium catalysts of general formula (Va) and (Vb), wherein: R 6is selected from the group consisting of phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl and 2,6-diethyl-4-methylphenyl; R 7 is hydrogen, R 8 is hydrogen or methyl, R 9 and R 10 are the same and are tert-butyl or cyclohexyl; m is 1.

[0059] The amount of iridium catalyst used is preferably in the range of 0.001 mol % to 5 mol %, more preferably 0.002 mol % to 4 mol %, most preferably 0.005 mol % to 3 mol %, and especially 0.01 mol % to 2.0 mol %, based on the amount of compound of formula (II).

[0060] Chiral iridium catalysts can be prepared by methods known in the art from an iridium(I) catalyst precursor, such as [Ir(COD)Cl]2, a chiral ligand of formula (IIIa), (IIIb), (IVa) or (IVb), and an alkali salt of a non-coordinating anion (S. Kaiser et al., Angew. Chem. Int. Ed. 2006, 45, 5194-5197; W. J. Drury III et al., Angew. Chem. Int. Ed. 2004, 43, 70-74).

[0061] Preferably, the process according to the invention is carried out in the presence of a chiral iridium catalyst and in the presence of an additive, wherein the chiral iridium catalyst is selected from the group consisting of [IrL*(COD)]Y and [IrL*(nbd)]Y, L* is a chiral ligand of formula (IIIa), (IIIb), (IVa) or (IVb), COD stands for 1,5-cyclooctadiene nbd represents norbornadiene, and Y is [B(R 18 )4] - , PF6 - , SbF6 - , CF3SO3 - a non-coordinating anion selected from the group consisting of [Al{OC(CF3)3}4]- (formula (VII)) and Δ-TRISPHAT (formula (VIII)), [ka] [In the formula, R 18 is selected from fluorine and phenyl, which is unsubstituted or substituted by 1 to 5 substituents selected from C1-C4-alkyl, C1-C4-haloalkyl and halogen. Here, the additives include hexafluorophosphoric acid, acetic acid, trifluoromethylsulfonic acid, water, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, tetrafluoroboric acid, tetrafluoroboric acid diethyl ether complex, Nafion, Amberlyst, 1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, borane tetrahydro The boron trifluoride complex is preferably selected from the group consisting of boron trifluoride diethyl ether complex, boron trifluoride acetate complex and boron trifluoride n-propanol complex, and mixtures thereof.

[0062] More preferably, the process according to the invention is carried out in the presence of a chiral iridium catalyst and in the presence of an additive, wherein said chiral iridium catalyst is selected from the group consisting of chiral iridium catalysts of formula [IrL*(COD)]Y and [IrL*(nbd)]Y, wherein L* is a chiral ligand of formula (IIIa), (IIIb), (IVa) or (IVb), COD stands for 1,5-cyclooctadiene nbd represents norbornadiene, and Y is PF, [Al{OC(CF3)3}4]- (formula (VII)) or [B(R 18 )4] - represents Here, R 18 is phenyl, which is unsubstituted or substituted by 1 to 5 substituents selected from fluorine and trifluoromethyl; Wherein, the additive is selected from the group consisting of hexafluorophosphoric acid, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, tetrafluoroborate diethyl ether complex, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof, wherein the complexes of boron trifluoride are preferably selected from boron trifluoride-diethyl ether complex, boron trifluoride acetate complex, and boron trifluoride n-propanol complex.

[0063] Even more preferably, the process according to the invention is carried out in the presence of a chiral iridium catalyst and in the presence of an additive, wherein the chiral iridium catalyst is selected from the group consisting of chiral iridium catalysts of formula (Va), (Vb), (VIa) and (VIb); [ka] [During the ceremony, R 6 is selected from the group consisting of 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl, or phenyl; wherein 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl and phenyl are unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkoxy, C1-C4-alkyl, C1-C4-haloalkyl and phenyl, wherein the phenyl is also unsubstituted or substituted by 1 to 5 C1-C6-alkyl substituents, R 7 and R 8 are, independently of one another, hydrogen, C1-C6-alkyl or C1-C6-alkoxy, R 9 and R 10 are each independently selected from the group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl; m is 1 or 2; R 13 is iso-propyl, sec-butyl, iso-butyl, tert-butyl, phenyl or benzyl, R 14 and R 15 are independently selected from the group consisting of C1-C6-alkyl and C6-aryl-C1-C4-alkyl, Here, the C6-C 14 -C6-aryl in the aryl-C1-C4-alkyl moiety is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen and C1-C4-alkyl, R16 and R 17 are, independently of each other, phenyl, 1-naphthyl or 2-naphthyl, They are, in each case, unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-haloalkyl, and R 18 is phenyl, which is unsubstituted or substituted by 1 to 5 substituents selected from fluorine and C1-C4-haloalkyl; Wherein, the additive is selected from the group consisting of hexafluorophosphoric acid, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof, wherein the boron trifluoride complex is preferably selected from the group consisting of boron trifluoride-diethyl ether complex, boron trifluoride acetate complex, and boron trifluoride n-propanol complex.

[0064] Particularly preferably, the process according to the invention is carried out in the presence of a chiral iridium catalyst and in the presence of an additive, wherein said chiral iridium catalyst is selected from the group consisting of the chiral iridium catalysts of formulae (Va), (Vb), (VIa) and (VIb), wherein R 6is selected from the group consisting of phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl and 2,6-diethyl-4-methylphenyl; R 7 is hydrogen, R 8 is hydrogen or methyl, R 9 and R 10 are each the same and are tert-butyl, adamantyl, cyclopentyl, or cyclohexyl; m is 1 or 2; R 13 is tert-butyl, R 14 and R 15 is methyl, R 16 and R 17 are, independently of one another, phenyl, which is substituted by one or two methyls, in particular R 16 and R 17 are each the same and are 2-methylphenyl or 3,5-dimethylphenyl, and R 18 is 3,5-bis(trifluoromethyl)phenyl, Wherein, the additive is selected from the group consisting of aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, tris(2,3,4,5,6-pentafluorophenyl)borane, hexafluorophosphoric acid, boron trifluoride, and a complex of boron trifluoride, wherein the boron trifluoride complex is preferably selected from the group consisting of boron trifluoride-diethyl ether complex, boron trifluoride acetate complex, and boron trifluoride n-propanol complex.

[0065] The process according to the invention involves the enantioselective hydrogenation of a compound of formula (II).

[0066] Preferably, the hydrogenation is carried out with hydrogen gas at a pressure of 1-300 bar, preferably 3-200 bar, most preferably 20-150 bar.

[0067] The hydrogenation is carried out at a temperature within the range of preferably 20°C to 130°C, more preferably 30°C to 100°C.

[0068] Suitable solvents are halogenated alcohols such as 2,2,2-trifluoroethanol, hexafluoroisopropanol (1,1,1,3,3,3-hexafluoro-2-propanol) and tetrafluoropropanol (2,2,3,3-tetrafluoro-1-propanol), halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane and trichloroethane, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane and anisole, and esters such as ethyl acetate, isopropyl acetate, and mixtures thereof.

[0069] Preferred solvents are selected from the group consisting of 2,2,2-trifluoroethanol, hexafluoroisopropanol, 1,2-dichloroethane, tetrafluoropropanol, 1,4-dioxane, isopropyl acetate, toluene, and mixtures thereof.

[0070] More preferred solvents are selected from the group consisting of 2,2,2-trifluoroethanol, hexafluoroisopropanol, 1,2-dichloroethane, tetrafluoropropanol, and mixtures thereof.

[0071] Particularly preferred are 2,2,2-trifluoroethanol and hexafluoroisopropanol.

[0072] Most preferred is hexafluoroisopropanol.

[0073] Abbreviations and acronyms: TIFF0007598369000017.tif91170

[0074] Preparation of iridium catalyst [ka] The ligand precursors (enantiomerically enriched secondary alcohols) were prepared according to known literature procedures such as those disclosed in S. Kaiser et al., Angew. Chem. Int. Ed. 2006, 45, 5194-5197 or DH Woodmansee Chem. Sci 2010, 1, 72. The ligands and iridium complexes were prepared by modified procedures based on the same literature precedents:

[0075] Standard Procedure Procedure for the ligand synthesis (under Ar): A solution of the alcohol precursor in THF (0.25 mmol, in 5.0 mL of THF) was cooled to -78 °C and n-BuLi (0.1 mL of a 2.5 M solution of n-BuLi in hexanes; 0.25 mmol; 1 equiv.) was added dropwise to the continuously stirred solution. After the addition was complete, the solution was allowed to warm to room temperature and stirred at this temperature for an additional 30 min. The solution was cooled again to -78 °C and R2PCl (0.25 mmol, 1 equiv.) was added to the continuously stirred solution. The mixture was allowed to warm to room temperature and was subsequently heated to 50 °C and kept at this temperature overnight. 31 The theoretical yield of the ligand was calculated using P-NMR, and the ligand was used in the next step without further purification.

[0076] Complexation procedure (under Ar): To the crude ligand solution was added [Ir(COD)2]BARF (BARF = tetrakis[3,5-bis(trifluoromethyl)phenyl]-borate) (as a solid, 1 equivalent based on theoretical yield). The resulting mixture was heated to 50 °C and kept at this temperature for 3 h.

[0077] Workup (under air): After cooling to room temperature, the reaction solution was rotary evaporated onto silica and loaded onto a column of silica. Minor components were eluted with pentane / diethyl ether, followed by the desired complex with DCM. The solvent was then evaporated under reduced pressure.

[0078] The following catalysts were synthesized and characterized: [ka] m=1 and R 18 = 3,5-Bis(trifluoromethyl)phenyl

[0079] [Table 1]

[0080] Va-2 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (89.5 mg, 53% based on [Ir(COD)2]BARF).

[0081] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.26 (dd, J = 7.9, 1.7 Hz, 2H), 7.81 - 7.36 (m, 16H), 5.75 (dt, J = 8.0, 5.2 Hz, 1H), 5.34 - 5.29 (m, 1H), 4.51 (q, J = 5.3, 3.2 Hz, 1H), 4.11 (dq, J = 12.5, 7.6, 5.9 Hz, 1H), 3.08 (ddd, J = 16.6, 10.3, 3.8 Hz, 1H), 2.99 - 2.70 (m, 2H), 2.61 - 2.00 (m, 8H), 1.92 - 1.79 (m, 1H), 1.69 (dd, J = 14.8, 8.1 Hz, 1H), 1.51 (s, 9H), 1.29 - 1.24 (m, 3H), 1.06 (d, J = 14.4 Hz, 9H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 142.09. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.85. HR-MS (ESI) m / z calcd for C 31 H 44 NOPIr[M]+ 670.2790 found 670.2798.

[0082] Va-4 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (241 mg, 71% based on [Ir(COD)2]BARF).

[0083] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.38 - 8.14 (m, 2H), 7.83 - 7.43 (m, 16H), 5.76 (dt, J = 7.7, 4.9 Hz, 1H), 4.81 (t, J = 7.6 Hz, 1H), 4.70 - 4.46 (m, 1H), 3.56 - 3.39 (m, 1H), 3.06 (ddd, J = 16.7, 10.3, 3.6 Hz, 1H), 2.98 - 2.73 (m, 2H), 2.71 - 2.57 (m, 1H), 2.44 (s, 3H), 2.41 - 2.02 (m, 6H), 2.00 - 1.75 (m, 7H), 1.72 - 1.54 (m, 4H), 1.46 - 0.94 (m, 13H), 0.72 - 0.50 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 121.27. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.86. HR-MS (ESI) m / z calcd for C 35 H 48 NOPIr[M]+ 722.3103 found 722.3116.

[0084] Vb-5 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex was isolated as an orange solid (261 mg; 74% based on [Ir(COD)2]BARF).

[0085] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.25 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.1 Hz, 1H), 7.81 - 7.64 (m, 11H), 7.56 (s, 4H), 5.74 (dt, J = 8.2, 4.6 Hz, 1H), 4.95 - 4.74 (m, 1H), 4.74 - 4.51 (m, 1H), 3.60 - 3.45 (m, 1H), 3.23 - 2.91 (m, 2H), 2.90 - 2.70 (m, 1H), 2.67 - 2.50 (m, 1H), 2.52 - 2.23 (m, 4H), 2.28 - 2.04 (m, 3H), 2.04 - 1.77 (m, 7H), 1.69 - 1.58 (m, 4H), 1.45 - 1.26 (m, 17H), 1.17 - 0.95 (m, 4H), 0.68 - 0.42 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 121.12. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = - 62.85. HR-MS (ESI) m / z calcd for C 38 H 54 NOPIr[M]+ 764.3572 found 764.3586.

[0086] Va-6 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (286 mg, 64% based on [Ir(COD)2]BARF). 1H-NMR (300 MHz, CDCl3): δ (ppm) = 8.20 (d, J = 8.2 Hz, 2H), 7.77 - 7.69 (m, 8H), 7.66 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 4.9 Hz, 5H), 5.77 - 5.67 (m, 1H), 4.78 (d, J = 7.6 Hz, 1H), 4.57 (s, 1H), 3.47 (s, 1H), 3.08 - 2.89 (m, 1H), 2.89 - 2.66 (m, 2H), 2.59 (p, J = 7.4 Hz, 1H), 2.47 - 1.74 (m, 15H), 1.42 (s, 17H), 1.18 - 0.78 (m, 5H), 0.72 - 0.48 (m, 1H). 31 P-NMR (122 MHz, CDCl3) 121.31. 19 F-NMR (282 MHz, CDCl3) δ = - 62.42. HR-MS (ESI): m / z calculated for [C 39 H 56 NOP193Ir]+: 778.3729 found 778.3732.

[0087] Vb-7 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex could be isolated after two purification steps as an orange solid (151 mg; 36% based on [Ir(COD)2]BARF).

[0088] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.84 (s, 1H), 8.38 - 8.27 (m, 1H), 8.21 (ddt, J = 8.5, 1.3, 0.7 Hz, 1H), 8.18 - 8.02 (m, 2H), 7.83 - 7.72 (m, 10H), 7.72 - 7.54 (m, 6H), 7.49 (ddd, J = 8.8, 6.6, 1.4 Hz, 1H), 7.23 - 6.96 (m, 1H), 5.74 - 5.54 (m, 1H), 5.26 - 5.12 (m, 1H), 4.41 - 4.18 (m, 1H), 3.53 - 3.15 (m, 3H), 2.75 - 2.61 (m, 2H), 2.59 - 2.32 (m, 2H), 2.18 - 1.91 (m, 6H), 1.92 - 1.74 (m, 5H), 1.74 - 1.56 (m, 2H), 1.48 - 1.21 (m, 10H), 1.18 - 0.99 (m, 1H), 0.96 - 0.59 (m, 2H), 0.39 - 0.15 (m, 1H), 0.06 - -0.11 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 120.30. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.87. HR-MS (ESI) m / z calcd for C 42 H 50 NOPIr [M]+ 808.3259 found 808.3278.

[0089] Va-8 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex was isolated using DCM (100%) to give an orange solid (296 mg; 78% based on [Ir(COD)2]BARF).

[0090] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.68 (s, 1H), 8.23 ​​- 7.85 (m, 3H), 7.75 - 7.23 (m, 17H), 7.05 (dq, J = 8.8, 1.0 Hz, 1H), 5.61 - 5.40 (m, 2H), 5.12 - 4.88 (m, 1H), 4.24 - 4.00 (m, 1H), 3.25 - 2.88 (m, 3H), 2.58 - 2.46 (m, 2H), 2.44 - 2.14 (m, 7H), 2.08 - 1.61 (m, 11H), 1.61 - 1.37 (m, 5H), 1.37 - 1.07 (m, 6H), 1.03 - 0.85 (m, 1H), 0.65 - 0.45 (m, 1H), 0.16 (dtd, J = 15.8, 10.4, 5.6 Hz, 1H), -0.16 (dt, J = 13.2, 9.1 Hz, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ = 120.57. 19 F-NMR (282 MHz, CD2Cl2) δ = -62.86. HR-MS (ESI) m / z calcd for C 43 H 52 NOPIr [M]+ 822.3416 found 822.3416.

[0091] Va-9 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex was isolated as an orange solid (298 mg, 82% based on [Ir(COD)2]BARF).

[0092] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 7.80 - 7.52 (m, 12H), 7.42 - 7.19 (m, 3H), 7.12 (d, J = 7.5 Hz, 1H), 5.65 (td, J = 5.6, 2.6 Hz, 1H), 5.48 - 5.42 (m, 1H), 4.43 - 4.37 (m, 1H), 3.38 - 3.30 (m, 1H), 3.21 - 2.89 (m, 3H), 2.67 (s, 3H), 2.58 - 2.45 (m, 2H), 2.42 (s, 3H), 2.38 - 2.16 (m, 2H), 2.13 - 2.05 (m, 3H), 2.02 - 1.89 (m, 4H), 1.84 (s, 3H), 1.81 - 1.72 (m, 2H), 1.64 - 1.49 (m, 3H), 1.39 - 1.19 (m, 8H), 1.12 - 0.99 (m, 4H), 0.68 - 0.56 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ = 118.80. 19 F-NMR (282 MHz, CD2Cl2) δ = -62.88. HR-MS (ESI) m / z calcd for C 37 H 52 NOPIr [M]+ 750.3416 found 750.3420.

[0093] Va-10 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex was isolated as an orange solid (148 mg, 40% based on [Ir(COD)2]BARF).

[0094] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 7.91-7.46 (m, 12H), 7.21 (s, 1H), 7.09 (s, 1H), 6.94 (s, 1H), 5.67 - 5.63 (m, 1H), 5.46 - 5.41 (m, 1H), 4.38 - 4.36 (m, 1H), 3.36 - 3.32 (m, 1H), 3.19 - 2.85 (m, 3H), 2.64 (s, 3H), 2.53 - 2.46 (m, 2H), 2.41 (s, 3H), 2.35 (s, 3H), 2.31 - 2.18 (m, 2H), 2.19 - 1.83 (m, 14H), 1.68 - 1.54 (m, 6H), 1.38 - 1.20 (m, 5H), 1.14 - 0.97 (m, 5H), 0.68 - 0.56 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ = 118.64. 19 F-NMR (282 MHz, CD2Cl2) δ = -62.87. HR-MS (ESI) m / z calcd for C 38 H 54 NOPIr[M]+ 764.3572 found 764.3577.

[0095] Va-11 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex was isolated using DCM (100%) to give an orange solid (310 mg; 85% based on [Ir(COD)2]BARF).

[0096] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 7.86 (s, 2H), 7.79 - 7.47 (m, 13H), 7.36 (s, 1H), 5.79 - 5.62 (m, 1H), 4.78 - 4.74 (m, 1H), 4.57 - 4.53 (m, 1H), 3.56 - 3.48 (m, 1H), 3.13 - 2.95 (m, 1H), 2.95 - 2.61 (m, 3H), 2.51 (s, 6H), 2.47 - 2.36 (m, 5H), 2.34 - 2.03 (m, 5H), 2.03 - 1.77 (m, 7H), 1.71 - 1.47 (m, 7H), 1.45 - 1.19 (m, 5H), 1.19 - 0.98 (m, 4H), 0.70 - 0.62 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ = 121.65. 19 F-NMR (282 MHz, CD2Cl2) δ = -62.88. HR-MS (ESI) m / z calcd for C 37 H 52 NOPIr[M]+ 750.3416 found 750.3406.

[0097] Va-12 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex was isolated as an orange solid (286 mg, 78% based on [Ir(COD)2]BARF).

[0098] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.61 - 8.48 (m, 1H), 8.28 - 8.15 (m, 1H), 8.11 - 7.98 (m, 1H), 7.98 - 7.81 (m, 1H), 7.79 - 7.50 (m, 16H), 5.70 (ddd, J = 8.1, 4.9, 3.2 Hz, 1H), 5.37 - 5.25 (m, 1H), 4.79 (d, J = 10.4 Hz, 1H), 3.53 - 3.41 (m, 1H), 3.13 (ddd, J = 17.2, 9.5, 4.9 Hz, 1H), 2.96 (ddd, J = 17.1, 9.4, 4.9 Hz, 1H), 2.88 - 2.66 (m, 1H), 2.49 - 2.34 (m, 7H), 2.27 - 2.14 (m, 1H), 2.09 - 1.56 (m, 15H), 1.43 - 1.12 (m, 9H), 1.06 - 0.92 (m, 1H), 0.78 - 0.59 (m, 1H), 0.42 - 0.25 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ = 121.69. 19 F-NMR (282 MHz, CD2Cl2) δ = -62.87. HR-MS (ESI) m / z calcd for C 39 H 50 NOPIr [M]+ 722.3259 found 722.3262.

[0099] Va-13 The reaction was carried out according to the standard procedure described above. The theoretical yield of the ligand was 51%. The complex could be isolated as an orange solid (78.0 mg, 39% based on [Ir(COD)2]BARF).

[0100] 1H-NMR (300 MHz, CDCl3): δ (ppm) = 8.22 (d, J = 8.7 Hz, 2H), 7.80 - 7.63 (m, 8H), 7.63 - 7.43 (m, 5H), 7.16 (d, J = 8.8 Hz, 2H), 5.82 - 5.66 (m, 1H), 5.37 - 5.22 (m, 1H), 4.56 - 4.41 (m, 1H), 4.18 - 4.00 (m, 1H), 3.93 (s, 3H), 3.12 - 2.97 (m, 1H), 2.96 - 2.74 (m, 2H), 2.70 - 2.56 (m, 1H), 2.43 (s, 3H), 2.41 - 2.03 (m, 4H), 1.96 - 1.84 (m, 1H), 1.72 (dd, J = 14.6, 7.9 Hz, 1H), 1.51 (d, J = 15.0 Hz, 9H), 1.34 - 1.23 (m, 3H), 1.05 (d, J = 14.4 Hz, 9H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 141.86. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.85. HR-MS (ESI) m / z calcd for C 32 H 46 NO2PIr [M]+ 700.2895 found 700.2899.

[0101] Va-14 287mg of [Ir(COD) 2 The reaction was carried out according to the standard procedure described above using ]BARF (0.225 mmol). The complex was obtained as an orange solid (245 mg; [Ir(COD) 2 ]BARF was isolated as 70%).

[0102] 1H-NMR (300 MHz, CDCl3): δ (ppm) = 8.38 - 8.12 (m, 2H), 7.82 - 7.63 (m, 8H), 7.51 (s, 5H), 7.44 - 7.17 (m, 2H), 5.81 - 5.63 (m, 1H), 4.81 - 4.67 (m, 1H), 4.67 - 4.49 (m, 1H), 3.57 - 3.35 (m, 1H), 3.05 - 2.90 (m, 1H), 2.88 - 2.61 (m, 3H), 2.36 (s, 3H), 2.31 - 2.04 (m, 7H), 2.01 - 1.73 (m, 7H), 1.70 -1.48 (m, 6H), 1.42 - 1.20 (m, 6H), 1.16 - 0.97 (m, 4H), 0.63 - 0.40 (m, 1H). 31 P-NMR (122 MHz, CDCl3) δ (ppm) = 121.31. 19 F-NMR (282 MHz, CDCl3) δ (ppm) = -62.43, -106.61. HR-MS (ESI) m / z calcd for C 35 H 47 NOFPIr [M]+ 740.3009 found 740.3013.

[0103] Va-15 The reaction was carried out according to the standard procedure described above using 287 mg of [Ir(COD)2]BARF (0.225 mmol). The complex was isolated as an orange solid (180.0 mg, 48% based on [Ir(COD)2]BARF).

[0104] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.46 (d, J = 7.9 Hz, 2H), 7.94 (d, J = 8.0 Hz, 2H), 7.82 - 7.38 (m, 13H), 5.83 - 5.69 (m, 1H), 4.94 - 4.78 (m, 1H), 4.73 - 4.54 (m, 1H), 3.65 - 3.38 (m, 1H), 3.15 - 2.72 (m, 3H), 2.61 - 2.27 (m, 7H), 2.25 - 2.04 (m, 4H), 2.04 - 1.72 (m, 8H), 1.75 - 1.58 (m, 3H), 1.43 - 1.22 (m, 8H), 1.19 - 0.93 (m, 1H), 0.63 - 0.44 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 121.74. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.88, -63.40. HR-MS (ESI) m / z calcd for C 36 H 47 NOF3PIr [M]+ 790.2977 found 790.2990.

[0105] Va-16 The reaction was carried out according to the standard procedure described above. The theoretical yield of the ligand was 90%. The complex could be isolated as an orange solid (261 mg, 75% based on [Ir(COD)2]BARF).

[0106] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 8.28 - 8.11 (m, 2H), 7.93 - 7.45 (m, 16H), 5.81 (dt, J = 9.3, 5.0 Hz, 1H), 4.89 (t, J = 6.9 Hz, 1H), 4.72 - 4.51 (m, 1H), 3.86 - 3.66 (m, 1H), 3.18 - 3.04 (m, 1H), 3.04 - 2.57 (m, 4H), 2.49 (s, 3H), 2.46 - 1.61 (m, 18H), 1.56 - 1.36 (m, 5H), 1.36 - 1.14 (m, 1H), 1.13 - 0.93 (m, 1H), 0.77 - 0.66 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 129.37. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.88. HR-MS (ESI) m / z calcd for C 33 H 44 NOPIr [M]+ 694.2790 found 694.2789.

[0107] Vb-17 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (134 mg; 95% purity based on 31P-NMR; 39% based on [Ir(COD)2]BARF).

[0108] 1H-NMR (300 MHz, CDCl3): δ (ppm) = 8.00 - 7.92 (m, 2H), 7.81 - 7.76 (m, 1H), 7.75 - 7.64 (m, 10H), 7.62 - 7.55 (m, 2H), 7.52 (d, J = 1.9 Hz, 4H), 5.88 (dt, J = 8.3, 4.9 Hz, 1H), 4.52 (dt, J = 8.3, 4.2 Hz, 1H), 4.37 (ddt, J = 7.4, 5.0, 2.5 Hz, 1H), 3.61 (td, J = 8.0, 3.8 Hz, 1H), 3.17 - 2.64 (m, 4H), 2.34 - 1.79 (m, 9H), 1.68 - 1.55 (m, 1H), 1.36 - 0.90 (m, 9H). 31 P-NMR (122 MHz, CDCl3) δ = 116.36 (major product; 95%), 111.79 (minor species; 5%). 19 F-NMR (282 MHz, CDCl3) δ = -62.41. HR-MS (ESI) m / z calcd for C 26 H 34 NOPIr [M]+ 600.2006 found 600.2006.

[0109] Va-18 The reaction was carried out according to the standard procedure described above (0.5 mmol scale), but after the addition of ClP(iPr)2 was completed, the reaction mixture was stirred at room temperature for 16 h. The complex could be isolated as an orange solid (605 mg, 85% based on [Ir(COD)2]BARF).

[0110] 1H-NMR (300 MHz, CDCl3): δ (ppm) = 8.17 (dd, J = 7.1, 1.8 Hz, 2H), 7.78 - 7.40 (m, 16H), 5.74 (dt, J = 9.0, 4.7 Hz, 1H), 4.83 (t, J = 6.9 Hz, 1H), 4.61 (dt, J = 8.7, 4.1 Hz, 1H), 3.62 - 3.53 (m, 1H), 3.11 - 2.94 (m, 1H), 2.91 - 2.67 (m, 2H), 2.67 - 2.44 (m, 2H), 2.39 (s, 3H), 2.36 - 1.93 (m, 6H), 1.85 (dd, J = 14.5, 7.3 Hz, 1H), 1.46 (dd, J = 15.2, 7.1 Hz, 3H), 1.39 - 1.31 (m, 1H), 1.23 (dd, J = 13.3, 6.9 Hz, 4H), 1.08 (dd, J = 19.4, 7.1 Hz, 3H), 0.52 (dd, J = 15.5, 7.1 Hz, 3H). 31 P-NMR (122 MHz, CDCl3) δ (ppm) = 129.53. 19 F-NMR (282 MHz, CDCl3) δ (ppm) = -62.42. HR-MS (ESI) m / z calcd for C 29 H 40 NOPIr[M]+ 642.2477 found 642.2480.

[0111] Va-19 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (249 mg, 73% based on [Ir(COD)2]BARF).

[0112] 1H-NMR (300 MHz, CD2Cl2): δ (ppm) = 7.81 - 7.61 (m, 9H), 7.56 (d, J = 2.0 Hz, 4H), 7.34 (d, J = 8.0 Hz, 1H), 5.76 (dt, J = 8.7, 4.5 Hz, 1H), 5.05 - 4.84 (m, 2H), 3.74 - 3.57 (m, 1H), 3.56 - 3.36 (m, 1H), 3.07 (s, 3H), 3.01 - 1.49 (m, 23H), 1.42 - 1.01 (m, 9H), 0.85 - 0.70 (m, 1H), 0.51 - 0.25 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 126.20. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.88. HR-MS (ESI) m / z calcd for C 29 H 44 NOPIr [M]+ 644.2766 found 644.2762.

[0113] Va-20 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (164 mg, 42% based on [Ir(COD)2]BARF).

[0114] 1 H-NMR (300 MHz, CD2Cl2): δ (ppm) = 7.86 - 7.62 (m, 10H), 7.56 (s, 4H), 7.38 (s, 1H), 5.72 (dt, J = 8.1, 5.2 Hz, 1H), 4.85 - 4.63 (m, 2H), 3.80 (s, 3H), 3.49 - 3.30 (m, 1H), 3.18 - 2.60 (m, 4H), 2.54 - 2.23 (m, 6H), 2.23 - 1.57 (m, 16H), 1.53 - 1.49 (m, 20H), 1.46 - 0.93 (m, 10H). 31P-NMR (122 MHz, CD2Cl2) δ (ppm) = 123.26. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.87. HR-MS (ESI) m / z calcd for C 44 H 66 NO2PIr [M]+ 864.4460 found 864.4448.

[0115] Va-21 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (51 mg, 14% based on [Ir(COD)2]BARF).

[0116] 1 H-NMR (400 MHz, CD2Cl2): δ (ppm) = 7.80 - 7.64 (m, 8H), 7.56 (s, 4H), 7.23 (s, 2H), 7.04 (s, 1H), 5.65 (dt, J = 5.9, 3.7 Hz, 1H), 5.45 - 5.35 (m, 1H), 4.04 (ddd, J = 8.2, 5.4, 3.6 Hz, 1H), 3.34 (dd, J = 11.2, 6.4 Hz, 1H), 3.19 - 3.08 (m, 3H), 3.06 - 2.89 (m, 2H), 2.56 - 2.44 (m, 2H), 2.41 (s, 3H), 2.33 - 1.84 (m, 9H), 1.84 - 1.43 (m, 15H), 1.35 - 1.24 (m, 12H), 1.23 - 1.14 (m, 5H), 1.09 (dd, J = 10.0, 6.8 Hz, 6H), 0.95 (d, J = 6.6 Hz, 3H), 0.60 - 0.46 (m, 1H). 31 P-NMR (162 MHz, CD2Cl2) δ (ppm) = 119.43. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.86. HR-MS (ESI) m / z calcd for C 44 H 66NOPIr[M]+ 848.4511 found 848.4512.

[0117] Va-22 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (274 mg, 73% based on [Ir(COD)2]BARF).

[0118] 1 H-NMR (300 MHz, CD2Cl2): δ (ppm) = 7.79 - 7.66 (m, 8H), 7.56 (s, 4H), 7.29 (s, 1H), 7.23 (s, 1H), 7.13 (s, 1H), 5.65 (td, J = 5.9, 2.2 Hz, 1H), 5.46 - 5.40 (m, 1H), 4.42 - 4.36 (m, 1H), 3.38 - 3.30 (m, 1H), 3.19 - 2.86 (m, 3H), 2.65 (s, 3H), 2.59 - 2.44 (m, 2H), 2.42 (s, 3H), 2.38 - 1.54 (m, 20H), 1.46 - 0.98 (m, 21H), 0.70 - 0.58 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 118.67. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.86. HR-MS (ESI) m / z calcd for C 41 H 60 NOPIr [M]+ 806.4042 found 806.4053.

[0119] Va-23 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (15.6 mg, 20% based on [Ir(COD)2]BARF).

[0120] 1H-NMR (300 MHz, CD2Cl2) δ = 8.43 - 8.36 (m, 2H), 7.92 - 7.85 (m, 1H), 7.81 - 7.69 (m, 12H), 7.68 - 7.53 (m, 4H), 5.73 - 5.65 (m, 1H), 5.50 - 5.43 (m, 1H), 4.58 - 4.43 (m, 2H), 3.25 - 3.12 (m, 1H), 3.08 - 2.94 (m, 1H), 2.92 - 2.77 (m, 1H), 2.72 - 1.45 (m, 40H). 19 F-NMR (282 MHz, CDCl3) δ = -62.42. 31 P-NMR (122 MHz, CD2Cl2) δ = 134.32. HR-MS (TOF) m / z calcd for C 42 H 54 NOPIr[M]+ 812.3572 found 812.3578.

[0121] Va-24 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (274 mg, 72% based on [Ir(COD)2]BARF).

[0122] 1 H-NMR (300 MHz, CD2Cl2) δ = 8.99 - 8.77 (m, 3H), 8.04 - 7.63 (m, 15H), 7.56 (s, 4H), 5.72 - 5.63 (m, 1H), 4.88 - 4.83 (m, 1H), 4.74 - 4.68 (m, 1H), 3.49 - 3.40 (m, 1H), 3.27 - 3.07 (m, 1H), 3.08 - 2.91 (m, 1H), 2.86 - 2.74 (m, 1H), 2.61 - 2.36 (m, 6H), 2.19 (ddd, J = 15.6, 13.8, 8.1 Hz, 1H), 2.11 - 1.11 (m, 25H), 0.99 - 0.66 (m, 3H). 31P-NMR (122 MHz, CD2Cl2) δ = 121.93. 19 F-NMR (282 MHz, CD2Cl2) δ = -62.86. HR-MS (ESI) m / z calcd for C 43 H 52 NOPIr [M] + 822.3410 found 822.3436.

[0123] Va-25 The reaction was carried out according to the standard procedure described above. The complex could be isolated as an orange solid (282 mg, 76% based on [Ir(COD)2]BARF).

[0124] 1 H-NMR (300 MHz, CD2Cl2): δ (ppm) = 7.73 (s, 8H), 7.56 (s, 4H), 7.23 (s, 1H), 7.14 (s, 1H), 7.00 (s, 1H), 5.62 (dd, J = 8.0, 5.6 Hz, 1H), 5.46-5.39 (m, 1H), 4.32 (dd, J = 7.4, 3.4 Hz, 1H), 3.36-3.27 (m, 1H), 3.19-3.06 (m, 2H), 3.01-2.91 (m, 2H), 2.80 (dq, J = 14.9, 7.4 Hz, 1H), 2.59-2.43 (m, 2H), 2.43-2.15 (m, 7H), 2.15-0.83 (m, 36H), 0.66-0.48 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ (ppm) = 119.00. 19 F-NMR (282 MHz, CD2Cl2) δ (ppm) = -62.87. HR-MS (ESI) m / z calcd for C40H58NOPIr [M] + 792.3880 found 792.3903.

[0125] Va-26 A solution of the respective alcohol precursor in THF (0.25 mmol, in 5.0 mL of THF) was cooled to -78 °C and n-BuLi (0.1 mL of 2.5 M n-BuLi solution in hexanes; 0.25 mmol; 1 equiv.) was added dropwise to the continuously stirred solution. After the addition was complete, the solution was warmed to room temperature and stirred at this temperature for an additional 30 min. The solution was cooled again to -78 °C and Cy2PCl (0.25 mmol, 1 equiv.) was added to the continuously stirred solution. The mixture was warmed to room temperature and subsequently heated to 50 °C and kept at this temperature overnight. After the reaction was cooled to room temperature, the THF was removed and dried under vacuum, [Ir(cod)Cl]2 (0.125 mmol) and DCM (5.0 ml) were added to the tube and stirred at 50 °C for 2 h. KPF6 (0.25 mmol) was then added and stirred at room temperature overnight. The reaction solution is rotary evaporated onto silica, loaded onto a column of silica prepared in DCM and chromatographed with EtOAc / DCM:1 / 10 to give an orange solid (130 mg, 55%) after two column chromatography runs.

[0126] 1 H-NMR (300 MHz, CD2Cl2) δ = 7.37 - 7.02 (m, 3H), 5.74 - 5.56 (m, 1H), 5.52 - 5.46 (m, 1H), 4.47 - 4.30 (m, 1H), 3.45 - 3.21 (m, 1H), 3.19 - 2.92 (m, 3H), 2.66 (s, 3H), 2.63 - 2.48 (m, 2H), 2.44 (s, 3H), 2.40 - 2.19 (m, 2H), 2.16 - 1.70 (m, 15H), 1.68 - 1.46 (m, 6H), 1.41 - 1.28 (m, 13H), 1.18 - 0.95 (m, 5H), 0.71 - 0.58 (m, 1H). 31 P-NMR (122 MHz, CD2Cl2) δ = 118.42, -127.01, -132.85, -138.70, -144.55, -150.39, -156.24, -162.09. 19F-NMR (376 MHz, CD2Cl2) δ = -72.64, -74.52. HR-MS (ESI) m / z calcd for C 41 H 60 NOPIr [M] + 806.4036 found 806.4061. EXAMPLES

[0127] The reactions were carried out in metal autoclaves. The reaction mixtures were analyzed via HPLC (Chiralpak IC column, 95 / 5 heptane / ethanol, 1 mL / min) or SFC (OZ-H column, 2.5% MeOH in supercritical CO2, 3 mL / min) chromatography without workup.

[0128] Ir-complex Va-25 (given catalyst loading) and 0.64 g of 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified by heptane:water washing + crystallization) were placed in an 8 mL autoclave vial containing a PTFE-coated stir bar. The autoclave vial was sealed using a screw cap with a septum and flushed with argon (10 min). Hexafluoroisopropanol (HFIP, 4 mL) and additives (given loading) were added to the vial through the septum. The vial was placed in an argon-containing autoclave and the autoclave was flushed with argon (10 min). The autoclave was pressurized three times with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure. After this, the autoclave was pressurized to 60 bar hydrogen pressure and placed in a suitable alumina block. After heating to 85° C., the reaction was kept at this temperature for the specified time. After cooling to room temperature and depressurization, the vials were removed from the autoclave and the reaction results were determined by GC-FID analysis (diluted with EtOH) and the enantiomeric excess was determined by HPLC analysis. Typical values ​​are shown.

[0129] [Table 2]

[0130] Examples 31 to 36: Ir-complex Va-25 (given catalyst loading) and 1-(2,2,4-trimethyl-1-quinolyl)ethanone (given amount; purified by heptane:water washing + crystallization) were placed in a 25 mL autoclave. The autoclave was flushed with argon (10 min). Hexafluoroisopropanol (1.33 mL per mmol of 1-(2,2,4-trimethyl-1-quinolyl)ethanone) and additives (given loading) were added to the autoclave. The autoclave was pressurized three times with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure. After this, the autoclave was pressurized to 60 bar hydrogen pressure and placed in a suitable alumina block. After heating to 85 °C, the reaction was kept at this temperature for the given time. After cooling to room temperature and depressurization, the reaction results were determined by GC-FID analysis (diluted with EtOH) and the enantiomeric excess was determined by HPLC analysis.

[0131] [Table 3]

[0132] Examples 37 to 54: The Ir complex (identifier and catalyst loading given) and 0.64 g of 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified by heptane:water washing + crystallization) were placed in an 8 mL autoclave vial containing a PTFE-coated stir bar. The autoclave vial was sealed using a screw cap with a septum and flushed with argon (10 min). Hexafluoroisopropanol (HFIP, 4 ml) and BF3*OEt2 (1 mol % with respect to 1-(2,2,4-trimethyl-1-quinolyl)ethanone) were added to the vial through the septum. The vial was placed in an argon-containing autoclave and the autoclave was flushed with argon (10 min). The autoclave was pressurized three times with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure. After this, the autoclave was pressurized to 60 bar hydrogen pressure and placed in a suitable alumina block. After heating to 85° C., the reaction was held at this temperature for a given time. After cooling to room temperature and depressurization, the vial was removed from the autoclave and the reaction results were determined by GC-FID analysis (diluted with EtOH) and the enantiomeric excess was determined by HPLC analysis. Typical values ​​are shown.

[0133] [Table 4]

[0134] Examples 55 to 58: Ir-complex Va-25 (0.02 mol%, 0.6 μmol) and 0.64 g of 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified by heptane:water washing + crystallization) were placed in an 8 mL autoclave vial containing a PTFE-coated stir bar. The autoclave vial was sealed using a screw cap with a septum and flushed with argon (10 min). 2,2,2-trifluoroethanol (TFE, 4 ml) and BF3*OEt2 (given charge) were added to the vial through the septum. The vial was placed in an argon-containing autoclave and the autoclave was flushed with argon (10 min). The autoclave was pressurized three times with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure. After this, the autoclave was pressurized to 60 bar hydrogen pressure and placed in a suitable alumina block. After heating to 85° C., the reaction was held at this temperature for 3 hours. After cooling to room temperature and depressurization, the vial was removed from the autoclave and the reaction results were determined by GC-FID analysis (diluted with EtOH) and the enantiomeric excess was determined by HPLC analysis. Typical values ​​are shown.

[0135] [Table 5]

[0136] Examples 59 and 60: The iridium catalyst (1) from DE112015001290 T5 is an example of a catalyst structure of formula (IXb). With this catalyst, the presence of BF3*OEt2 also has a strong effect on the conversion and a slightly positive effect on the ee (general conditions: 0.2 mol% of catalyst (I) from DE112015001290 T5, 40°C, 30 bar H2, starting material concentration 0.1 M in trifluoroethanol). [ka]

[0137] [Table 6]

Claims

1. Formula (Ia) or (Ib) [Formula 1] [During the ceremony, R １ is C 1 -C 6 -alkyl, R ２ and R ３ are identical and selected from C 1 -C 4 -alkyl, R ４ is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenyl or benzyl, n is 0, 1 or 2; Each of the substituents R ５ is, if present, independently selected from the group consisting of halogen, C 1 -C 6 -alkyl and C 1 -C 6 -haloalkyl. A method for preparing a compound of the formula: In the presence of a chiral iridium catalyst, and In the presence of additives Formula (II) [chemical 2] [In the formula, substituent R １ , R ２ , R ３ , R ４ , R ５ and integer n is as defined for compounds of formula (Ia) or (Ib), respectively. The method includes the enantioselective hydrogenation of a compound of the formula: The chiral iridium catalyst has the formula (IIIa), (IIIb), (IXa) or (IXb): [C3] [During the ceremony, R 6 is selected from the group consisting of 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl or phenyl, which is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of halogen, C 1 -C 4 -alkoxy, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl and phenyl, wherein said phenyl is also unsubstituted or substituted by 1 to 5 C 1 -C 6 -alkyl substituents, R 7 and R 8 are independently of each other hydrogen or C 1 -C 6 -alkyl, R ９ and R １０ are each independently selected from the group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl; m is 1 or 2; R １９ is phenyl or t-butyl, R ２０ is hydrogen or methyl, R ２１ are each independently selected from benzyl and methyl; R ２２ are each cyclohexyl. comprising a chiral ligand of The process according to claim 1, wherein the additive is selected from the group consisting of hexafluorophosphoric acid, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, triphenylborane, tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, aluminum(III) fluoride, titanium(IV) isopropoxide, trimethylaluminum, boron trifluoride, boron trifluoride-diethyl ether, boron trifluoride acetic acid, and boron trifluoride n-propanol, and mixtures thereof.

2. R １ But, C １ -C ４ - alkyl, R ２ and R ３ is methyl, R ４ But, C １ -C ４ - alkyl, n is 0 or 1; R ５ is fluorine, when present; and the chiral iridium catalyst is represented by formula (IIIa), (IIIb), (IXa) or (IXb): [C5] [During the ceremony, R ６ is selected from the group consisting of phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl or 2,6-diethyl-4-methylphenyl; R ７ is hydrogen, R ８ is hydrogen or methyl; R ９ and R １０ are each the same and selected from the group consisting of ethyl, iso-propyl, tert-butyl, cyclopentyl, adamantyl, and cyclohexyl; m is 1, R １９ is phenyl, R ２０ is methyl, R ２１ is benzyl, R ２２ is cyclohexyl. comprising a chiral ligand of 2. The method of claim 1, wherein the additive is selected from the group consisting of aluminum(III) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, tris(2,3,4,5,6-pentafluorophenyl)borane, hexafluorophosphoric acid, boron trifluoride, boron trifluoride-diethyl etherate, boron trifluoride acetic acid, and boron trifluoride n-propanol.

3. R １ is methyl, ethyl or n-propyl; R ２ and R ３ is methyl, R ４ But, C １ -C ４ - alkyl, n is 0, 1 or 2; Each of the substituents R ５ When present, halogen and C １ -C ６ 2. The method of claim 1, wherein each of the radicals is independently selected from the group consisting of: -alkyl.

4. The process according to any one of claims 1 to 3, wherein the hydrogenation is carried out with hydrogen gas at a pressure of from 1 to 300 bar.

5. The process according to any one of claims 1 to 3, wherein the amount of chiral iridium catalyst used is in the range of 0.001 mol % to 5 mol %, based on the amount of compound of formula (II).

6. The process according to any one of claims 1 to 3, wherein the hydrogenation is carried out at a temperature in the range of from 20°C to 130°C.

7. 4. The process according to any one of claims 1 to 3, wherein the hydrogenation is carried out in the presence of a solvent selected from the group consisting of 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, 1,2-dichloroethane, tetrafluoropropanol, and mixtures thereof.

8. The chiral iridium catalyst has the general formula (Va) or (Vb): [C6] [During the ceremony, R ６ is selected from the group consisting of 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl, or phenyl; wherein 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl and phenyl are unsubstituted or substituted with halogen, C １ -C ４ -Alkoxy, C １ -C ４ -Alkyl, C １ -C ４ -substituted by 1 to 5 substituents selected from the group consisting of haloalkyl and phenyl, wherein said phenyl is also unsubstituted or substituted by 1 to 5 C １ -C ６ - substituted by alkyl substituents, R ７ and R ８ are each independently hydrogen or C １ -C ６ - alkyl, R ９ and R １０ are each independently selected from the group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl; m is 1 or 2, and R １８ is phenyl, which is unsubstituted or contains fluorine and C １ -C ４ -haloalkyl; 2. The method of claim 1, comprising:

9. R ６is selected from the group consisting of phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl or 2,6-diethyl-4-methylphenyl; R ７ is hydrogen, R ８ is hydrogen or methyl; R ９ and R １０ are each the same and are tert-butyl, adamantyl, cyclopentyl, or cyclohexyl; m is 1 or 2, and R １８ The method of claim 8, wherein is 3,5-bis(trifluoromethyl)phenyl.

10. The chiral iridium catalyst has the formula (IIIa) or (IIIb): [During the ceremony, R ６ is selected from the group consisting of 1-naphthyl, 2-naphthyl, 9-anthracenyl, 9-phenanthryl or phenyl, which are unsubstituted or substituted with halogen, C １ -C ４ -Alkoxy, C １ -C ４ -Alkyl, C １ -C ４ -substituted by 1 to 5 substituents selected from the group consisting of haloalkyl and phenyl, wherein said phenyl is also unsubstituted or substituted by 1 to 5 C １ -C ６ - substituted by alkyl substituents, R ７ and R ８ are each independently hydrogen or C １ -C ６- alkyl, R ９ and R １０ are each independently selected from the group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl; and m is 1 or 2. The method of claim 1 , comprising a chiral ligand of the formula:

11. R ６ is selected from the group consisting of phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 9-anthracenyl, 2,4,6-triisopropylphenyl, 9-phenanthryl or 2,6-diethyl-4-methylphenyl; R ７ is hydrogen, R ８ is hydrogen or methyl; R ９ and R １０ are each the same and are tert-butyl, cyclopentyl, or cyclohexyl; The method of claim 10 , wherein m is 1.

12. The method according to any of claims 1 to 3, wherein the amount of additive used is in the range of 0.1 to 10 mol %, based on the amount of compound of formula (II).

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