IMPROVED ENANTIOSELECTIVE HYDROGENATION OF 4-SUBSTITUTED 1,2-DIHYDROQUINOLINES IN PRESENCE OF A CHIRAL IRIDIUM CATALYST AND AN ADDITIVE

Abstract

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

Claims

1. A process for preparing a compound of formula (Ta) or (Ib), ##STR00019## wherein R.sup.1 is selected from the group consisting of C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.6-C.sub.14-aryl, or C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl and the C.sub.1-C.sub.6-alkoxy in the C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl moiety, are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-haloalkoxy and phenyl, wherein the phenyl may be substituted by one to five substituents selected independently from each other from halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkyl, and C.sub.1-C.sub.4-haloalkoxy, and wherein the C.sub.6-C.sub.14-aryl and the C.sub.6-C.sub.14-aryl in the C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl moiety in each case is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, R.sup.2 and R.sup.3 are the same and are selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl and C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, or R.sup.2 and R.sup.3 together with the carbon which they are bound to, form a C.sub.3-C.sub.6-cycloalkyl ring, R.sup.4 is hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylamino, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.6-alkenyloxy, 9-flurorenylmethyleneoxy, C.sub.6-C.sub.14-aryl, C.sub.6-C.sub.14-aryloxy, C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyloxy or C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.6-C.sub.14-aryl as such or as part of a composite substituent is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, n is 0, 1, 2, 3 or 4, each substituent R.sup.5, if present, is independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, hydroxyl, amino and —C(═O)—C.sub.1-C.sub.6-alkyl, comprising enantioselective hydrogenation of a compound of the formula (II) ##STR00020## wherein the substituents R.sup.1, R.sup.2, R.sup.3, R.sup.4, R and the integer n are each as defined for the compound of the formula (Ia) or (Ib), in presence of a chiral iridium catalyst, wherein the chiral iridium catalyst comprises a chiral ligand of formula (IIIa), (IIIb), (IVa), (IVb), (IXa) or (IXb), ##STR00021## wherein R.sup.6, R.sup.7 and R.sup.8 are independently from one another selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.6-C.sub.14-aryl and C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.7-cycloalkyl and the C.sub.3-C.sub.7-cycloalkyl in the C.sub.3-C.sub.7-cycloalkyl-C.sub.1-C.sub.4-alkyl moiety are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkyl and C.sub.1-C.sub.4-haloalkoxy, and wherein the C.sub.6-C.sub.14-aryl and the C.sub.6-C.sub.14-aryl in the C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl moiety are optionally substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy and phenyl, wherein the phenyl again is unsubstituted or substituted by one to five C.sub.1-C.sub.6-alkyl substituents, R.sup.9 and R.sup.10 are independently from one another selected from the group consisting of C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy, di(C.sub.1-C.sub.6-alkyl)amino, C.sub.3-C.sub.12-cycloalkyl, C.sub.3-C.sub.12-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.6-C.sub.14-aryl, C.sub.6-C.sub.14-aryloxy and C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy and di(C.sub.1-C.sub.6-alkyl)amino, are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-haloalkoxy and phenyl, wherein the phenyl may be substituted by one to five substituents selected independently from each other from halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkyl, and C.sub.1-C.sub.4-haloalkoxy, and wherein the C.sub.6-C.sub.14-aryl, C.sub.6-C.sub.14-aryloxy and C.sub.3-C.sub.12-cycloalkyl, in each case as such or as part of a composite substituent, are optionally substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy and phenyl, wherein the phenyl is unsubstituted or substituted by one to five C.sub.1-C.sub.6-alkyl substituents or R.sup.9 and R.sup.10 together with the phosphorus atom which they are bound to, form a phospholane ring, which may be substituted with one or two C.sub.1-C.sub.6-alkyl groups, or R.sup.9 and R.sup.10 together form ##STR00022## in which the bonds identified by “x” and “y” are both bound directly to the phosphorus atom, p and q are independently from one another selected from 0, 1 and 2, R.sup.11 and R.sup.12 are independently selected from C.sub.1-C.sub.6-alkyl and phenyl, which may be substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy and phenyl, which may be substituted by one or two C.sub.1-C.sub.4-alkyl substituents, m is 1 or 2, A is ##STR00023## in which the bond identified by “*” is bound directly to the phosphorus atom and in which the bond identified by “#” is bound directly to the oxazoline moiety, R.sup.13 is C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.12-cycloalkyl, C.sub.3-C.sub.12-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.7-cycloalkyl, C.sub.6-C.sub.14-aryl or C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.6-C.sub.14-aryl and the C.sub.6-C.sub.14-aryl in the C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl moiety in each case is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, R.sup.14 and R.sup.15 are independently from one another selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.12-cycloalkyl, C.sub.3-C.sub.7-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.7-cycloalkyl, C.sub.6-C.sub.14-aryl and C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.6-C.sub.14-aryl and the C.sub.6-C.sub.14-aryl in the C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl moiety in each case is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, or R.sup.14 and R.sup.15 together with the carbon which they are bound to, form a C.sub.5-C.sub.6-cycloalkyl ring, R.sup.16 and R.sup.17 are independently from one another selected from the group consisting of C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy, di(C.sub.1-C.sub.6-alkyl)amino, C.sub.3-C.sub.12-cycloalkyl, C.sub.3-C.sub.12-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.6-C.sub.14-aryl, C.sub.6-C.sub.14-aryloxy and C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-cycloalkyl and di(C.sub.1-C.sub.6-alkyl)amino, are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-haloalkoxy and phenyl, wherein the phenyl may be substituted by one to five substituents selected independently from each other from halogen, C.sub.1-C.sub.4-alkyl, phenyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkyl, and C.sub.1-C.sub.4-haloalkoxy, and wherein the C.sub.6-C.sub.14-aryl, the C.sub.6-C.sub.14-aryl in the C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, the C.sub.6-C.sub.14-aryloxy and C.sub.3-C.sub.12-cycloalkyl, in each case as such or as part of a composite substituent, are optionally substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, phenyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, or R.sup.16 and R.sup.17 together with the phosphorus atom which they are bound to, form a phospholane ring, which may be substituted with one or two C.sub.1-C.sub.6-alkyl groups, or R.sup.16 and R.sup.17 together form ##STR00024## in which the bonds identified by “x” and “y” are both bound directly to the phosphorus atom, p and q are independently from one another selected from 0, 1 and 2, and R.sup.11 and R.sup.12 are independently selected from C.sub.1-C.sub.6-alkyl and phenyl, which may be substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy and phenyl, which may be substituted by one or two C.sub.1-C.sub.4-alkyl substituents, R.sup.19 are independently selected from phenyl, benzyl, t-butyl, isopropyl, cyclohexyl, R.sup.20 are independently selected from hydrogen, methyl, ethyl, isopropyl, R.sup.21 are independently selected from hydrogen, benzyl, methyl, ethyl, R.sup.22 are independently selected from cyclohexyl, phenyl, 2-methylphenyl, 4-methylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, and in the presence of an additive, wherein the additive is selected from the group consisting of Bronsted acids, Lewis acids, and mixtures thereof.

2. The process according to claim 1, wherein 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 diethylether 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 tetra-hydrofurane complex, boric acid, aluminum (III) trifluoromethanesulfonate, zinc (II) trifluoro-methanesulfonate, scandium (III) trifluoromethanesulfonate, aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof.

3. 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[3,5-bis(trifluoromethyl)phenyl]borane, tris(2,3,4,5,6-pentafluoro-phenyl)borane, aluminum (III) trifluoromethanesulfonate, scandium (III) trifluoromethane-sulfonate, aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof.

4. The process according to claim 1, wherein R.sup.1 is C.sub.1-C.sub.6-alkyl, R.sup.2 and R.sup.3 are the same and are selected from C.sub.1-C.sub.4-alkyl, R.sup.4 is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, phenyl or benzyl, n is 0, 1 or 2, each substituent R.sup.5, if present, is independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-haloalkyl, R.sup.6 is selected from the group consisting of 1-naphtyl, 2-naphtyl, 9-antracenyl, 9-phenantryl or phenyl, which is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl and phenyl, wherein the phenyl again is unsubstituted or substituted by one to five C.sub.1-C.sub.6-alkyl substituents, R.sup.7 and R.sup.8 are independently from one another hydrogen or C.sub.1-C.sub.6-alkyl, R.sup.9 and R.sup.10 are independently from one another 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, A is ##STR00025## in which the bond identified by “*” is bound directly to the phosphorus atom and in which the bond identified by “#” is bound directly to the oxazoline moiety, R.sup.13 is tert-butyl, iso-propyl or phenyl, R.sup.14 and R.sup.15 are methyl, R.sup.16 and R.sup.17 are each the same and 2-methylphenyl or 3,5-bismethylphenyl, R.sup.19 is phenyl, t-butyl, R.sup.20 is hydrogen, methyl, R.sup.21 is benzyl, methyl R.sup.22 is cyclohexyl, and wherein the additive is selected from the group consisting of hexafluorophosphoric acid, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, triphenylborane, tris[3,5-bis(trifluoro-methyl)phenyl]borane, tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum (III) trifluoromethane-sulfonate, scandium (III) trifluoromethanesulfonate, aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof.

5. The process according to claim 1, wherein R.sup.1 is C.sub.1-C.sub.4-alkyl, R.sup.2 and R.sup.3 are methyl, R.sup.4 is C.sub.1-C.sub.4-alkyl, n is 0 or 1 R.sup.5 if present, is fluorine, And wherein the chiral iridium catalyst comprises a chiral ligand of the formula (IIIa) or (IIIb), ##STR00026## wherein R.sup.6 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-dimethyl-phenyl, 4-fluorophenyl, 4-trifluoromehtylphenyl, 1-naphtyl, 9-antracenyl 2,4,6-triisopropylphenyl, 9-phenantryl or 2,6-diethyl-4-methylphenyl, R.sup.7 is hydrogen, R.sup.8 is hydrogen or methyl, R.sup.9 and R.sup.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.sup.19 is phenyl, R.sup.20 is methyl, R.sup.21 is benzyl, R.sup.22 is cyclohexyl, and wherein the additive is selected from the group consisting of aluminum (III) trifluoromethanesulfonate, scandium (III) trifluoromethanesulfonate, tris(2,3,4,5,6-pentafluorophenyl)borane, hexafluoro-phosphoric acid, boron trifluoride, boron trifluoride-diethylether complex, boron trifluoride acetic acid complex and boron trifluoride n-propanol complex.

6. The process according to claim 1, wherein R.sup.1 is C.sub.1-C.sub.6-alkyl or C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, wherein C.sub.6-C.sub.14-aryl in the C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl moiety is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, R.sup.2 and R.sup.3 are the same and are selected from C.sub.1-C.sub.4-alkyl, R.sup.4 is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, phenyl or benzyl, n is 0, 1 or 2, each substituent R.sup.5, if present, is independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-haloalkyl.

7. The process according to claim 1, wherein R.sup.1 is methyl, ethyl or n-propyl, R.sup.2 and R.sup.3 are methyl, R.sup.4 is C.sub.1-C.sub.4-alkyl, n is 0, 1 or 2, each substituent R.sup.5, if present, is independently selected from the group consisting of halogen and C.sub.1-C.sub.6-alkyl.

8. The process according to claim 1, wherein the hydrogenation is conducted using hydrogen gas at a pressure of from 1 to 300 bar.

9. The process according to claim 1, wherein the amount of chiral iridium catalyst used is within a range of from 0.001 mol % to 5 mol %, based on the amount of the compound of formula (II).

10. The process according to claim 1, wherein the hydrogenation is conducted at a temperature within a range of from 20° C. to 130° C.

11. The process according to claim 1, wherein the hydrogenation is conducted in 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.

12. The process according to claim 1, wherein the chiral iridium catalyst has formula (Va), (Vb), (VIa) or (VIb): ##STR00027## wherein R.sup.6 is selected from the group consisting of 1-naphtyl, 2-naphtyl, 9-antracenyl, 9-phenantryl or phenyl, wherein 1-naphtyl, 2-naphtyl, 9-antracenyl, 9-phenantryl and phenyl are unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl and phenyl, wherein the phenyl again is unsubstituted or substituted by one to five C.sub.1-C.sub.6-alkyl substituents, R.sup.7 and R.sup.8 are independently from one another hydrogen or C.sub.1-C.sub.6-alkyl, R.sup.9 and R.sup.10 are independently from one another 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.sup.13 is iso-propyl, sec-butyl, iso-butyl, tert-butyl, phenyl or benzyl, R.sup.14 and R.sup.5 are independently from one another selected from the group consisting of C.sub.1-C.sub.6-alkyl, and C.sub.6-aryl-C.sub.1-C.sub.4-alkyl, wherein the C.sub.6-aryl in the C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl moiety is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen and C.sub.1-C.sub.4-alkyl, R.sup.16 and R.sup.17 are independently from one another phenyl, 1-naphthyl or 2-naphthyl, which in each case is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkyl and C.sub.1-C.sub.4-haloalkyl, and R.sup.18 is phenyl, which is unsubstituted or substituted with one to five substituents selected from fluorine and C.sub.1-C.sub.4-haloalkyl.

13. The process according to claim 12, wherein R.sup.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-trifluoro-methylphenyl, 1-naphtyl, 9-antracenyl 2,4,6-triisopropylphenyl, 9-phenantryl or 2,6-diethyl-4-methylphenyl, R.sup.7 is hydrogen, R.sup.8 is hydrogen or methyl R.sup.9 and R.sup.10 are each the same and tert-butyl, adamantly, cyclopentyl or cyclohexyl, m is 1 or 2, R.sup.13 is tert-butyl, R.sup.14 and R.sup.15 are methyl, R.sup.16 and R.sup.17 are independently from one another phenyl, which is substituted by one or two methyl, optionally R.sup.16 and R.sup.17 are each the same and 2-methylphenyl or 3,5-dimethylphenyl, and R.sup.18 is 3,5-bis(trifluoromethyl)phenyl.

14. The process according to claim 1, wherein the chiral iridium catalyst comprises a chiral ligand of the formula (IIIa) or (IIIb), wherein R.sup.6 is selected from the group consisting of 1-naphtyl, 2-naphtyl, 9-antracenyl, 9-phenantryl or phenyl, which is unsubstituted or substituted by one to five substituents selected from the group consisting of halogen, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl and phenyl, wherein the phenyl again is unsubstituted or substituted by one to five C.sub.1-C.sub.6-alkyl substituents, R.sup.7 and R.sup.8 are independently from one another hydrogen or C.sub.1-C.sub.6-alkyl, R.sup.9 and R.sup.10 are independently from one another 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.

15. The process according to claim 14, wherein R.sup.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-trifluoro-methylphenyl, 1-naphtyl, 9-antracenyl 2,4,6-triisopropylphenyl, 9-phenantryl or 2,6-diethyl-4-methylphenyl, R.sup.7 is hydrogen R.sup.8 is hydrogen or methyl, R.sup.9 and R.sup.10 are each the same and tert-butyl, cyclopentyl or cyclohexyl, and m is 1.

16. The process according to claim 1, wherein the amount of additive used is within a range of from 0.1 to 10 mol %, based on the amount of the compound of formula (II).

Description

EXAMPLES

[0380] Reactions were performed in metal autoclaves. Reaction mixtures were analyzed without workup via HPLC (Chiralpak IC column, 95/5 heptane/ethanol, 1 mL/min) or SFC (OZ-H column, 2.5% MeOH in supercritical CO.sub.2, 3 mL/min) chromatography.

[0381] The Ir-complex Va-25 (catalyst loading given) and 0.64 g 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified with heptane: water wash+crystallization) were placed in an 8-mL autoclave vial containing a PTFE-coated stirring bar. The autoclave vial was closed using a screw cap with septum and flushed with argon (10 m5). Hexafluoroisopropanol (HFIP, 4 mL) and additive (loading given) were added via the septum to the vial. The vial was placed in an argon containing autoclave and the autoclave was flushed with argon (10 m). The autoclave was pressurized with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure three times. After this the autoclave was pressurized to 60 bar hydrogen pressure and was placed in a suitable alumina block. After heating to 85° C. the reaction was kept at this temperature for the given time.

[0382] After cooling to room temperature and depressurizing, the vial was taken out of the autoclave and the reactions outcome was determined by GC-FID analysis (deluted with EtOH) and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE-US-00003 TABLE 2 Additive Reaction catalyst loading Conversion Enantiomeric Example (mol %) time (h) (mol %) GC (% a/a) excess (% ee) 1 — 16 0.02 95.3 n.d. 2 — 21 0.02 95.5 n.d. 3 — 3 0.02 55.2 n.d. 4 — 16 0.03 97.6 n.d. 5 Pentafluorophenol (1) 16 0.02 97.2 n.d. 6 1,2,2,6,6-Pentamethylpiperidin (1) 16 0.02 67.1 n.d. 7 Nonafluoro-tert-butyl alcohol (1) 16 0.03 96.3 n.d. 8 Nonafluoro-tert-butyl alcohol (5) 16 0.03 97.5 n.d. 9 3,5-bis-trifluorophenol (1) 16 0.02 95.7 n.d. 10 AcOH (1) 16 0.02 96 n.d. 11 AcOH (5) 3 0.02 66.5 n.d. 12 AcOH (10) 3 0.02 63.7 n.d. 13 AcOH (20) 3 0.02 54.2 n.d. 14 HPF.sub.6 (1) 3 0.02 >99 n.d. 15 HBF.sub.4*OEt.sub.2 (1) 16 0.02 90.5 n.d. 16 TfOH (1) 16 0.02 76.9 n.d. 17 Sc(OTf).sub.3 (1) 3 0.02 >99 99 18 BF.sub.3*OEt.sub.2 (1) 3 0.02 98.9 98 19 BH.sub.3*THF (1) 3 0.02 69.8 n.d. 20 BF.sub.3*AcOH (1) 3 0.02 >99 n.d. 21 BF.sub.3*n-PrOH (1) 3 0.02 >99 n.d. 22 Al(OTf).sub.3 (1) 3 0.02 >99 n.d. 23 AlF.sub.3 (1) 3 0.02 65.9 n.d. 24 AlMe.sub.3 (1) 3 0.02 91.1 n.d. 25 Ti(O.sup.iPr).sub.4 (1) 3 0.02 90.7 n.d. 26 BPh.sub.3 (1) 3 0.02 85.4 n.d. 27 B(C.sub.6F.sub.5).sub.3 (1) 3 0.02 >99 97.6 28 B(C.sub.6F.sub.5).sub.3 (0.5) 3 0.02 97.3 n.d. 29 B(C.sub.6F.sub.5).sub.3 (0.1) 3 0.02 63.3 n.d. 30 B(OH).sub.3 (1) 3 0.02 72.7 n.d.

Examples 31-36

[0383] The Ir-complex Va-25 (catalyst loading given) and 1-(2,2,4-trimethyl-1-quinolyl)ethanone (amount given; purified with heptane: water wash+crystallization) were placed in an 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)ethenone)) and additive (loading given) were added to the autoclave. The autoclave was pressurized with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure three times. After this the autoclave was pressurized to 60 bar hydrogen pressure and was 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 depressurizing, the reactions outcome was determined by GC-FID analysis (deluted with EtOH) and the enantiomeric excess by HPLC analysis.

TABLE-US-00004 TABLE 3 Scale (amount catalyst Additive of compound Reaction loading Conversion Enantiomeric Example (mol %) (II)) time (h) (mol %) GC (% ala) excess (% ee) 31 —  9 mmol 6 0.01 50.8 n.d. 32 B(C.sub.6F.sub.5).sub.3 (0.5)  9 mmol 20 0.01 85.2 n.d. 33 BF.sub.3*OEt.sub.2 (1) 10 mmol 16 0.01 99.2 n.d. 34 Al(OTf).sub.3 (1) 10 mmol 16 0.01 >99 n.d. 35 HPF.sub.6 (1)  9 mmol 16 0.01 97.3 n.d. 36 BF.sub.3*AcOH (1)  9 mmol 16 0.01 98.1 n.d.

Examples 37-54

[0384] The Ir-complex (identifier and catalyst loading given) and 0.64 g 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified with heptane: water wash+crystallization) were placed in an 8-mL autoclave vial containing a PTFE-coated stirring bar. The autoclave vial was closed using a screw cap with septum and flushed with argon (10 min). Hexafluoroisopropanol (HFIP, 4 mL) and BF.sub.3*OEt.sub.2 (1 mol % with respect to 1-(2,2,4-trimethyl-1-quinolyl)ethanone) were added via the septum to the vial. The vial was placed in an argon containing autoclave and the autoclave was flushed with argon (10 min). The autoclave was pressurized with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure three times. After this the autoclave was pressurized to 60 bar hydrogen pressure and was 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 depressurizing, the vial was taken out of the autoclave and the reactions outcome was determined by GC-FID analysis (deluted with EtOH) and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE-US-00005 TABLE 4 catalyst Conversion Additive Reaction loading GC Enantiomeric Example Catalyst (mol %) time (h) (mol %) ( % a/a) excess (% ee) 37 Va-26 — 3 0.02 78.8 98.8 38 Va-26 BF.sub.3*OEt.sub.2 (1) 3 0.02 94.2 99 39 Va-22 — 3 0.02 85.2 98.5 40 Va-22 BF.sub.3*OEt.sub.2 (1) 3 0.02 >99 98.7 41 Va-15 — 16 0.025 9.4 n.d. 42 Va-15 — 16 0.05 34.6 83.2 43 Va-15 BF.sub.3*OEt.sub.2 (1) 16 0.025 82 89.2 44 Vb-7 — 16.5 0.025 79.5 97.5 45 Vb-7 BF.sub.3*OEt.sub.2 (1) 16 0.025 >99 98.3 46 Va-9 — 16.5 0.025 81.7 97.9 47 Va-9 BF.sub.3*OEt.sub.2 (1) 16 0.025 >99 98.8 48 Va-11 — 16.5 0.025 42.2 94.5 49 Va-11 BF.sub.3*OEt.sub.2 (1) 16 0.025 82.4 97.7 50 Va-21 — 16 0.025 74 98 51 Va-21 BF.sub.3*OEt.sub.2 (1) 16 0.025 >99 99.4 52 Vb-5 — 16 0.025 64.4 n.d. 53 Vb-5 — 16 0.05 98.4 96.8 54 Vb-5 BF.sub.3*OEt.sub.2 (1) 16 0.025 >99 97.7

Examples 55-58

[0385] The Ir-complex Va-25 (0.02 mol %, 0.6 mol) and 0.64 g 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified with heptane: water wash+crystallization) were placed in an 8-mL autoclave vial containing a PTFE-coated stirring bar. The autoclave vial was closed using a screw cap with septum and flushed with argon (10 min). 2,2,2-Trifluoroethanol (TFE, 4 mL) and BF.sub.3*OEt.sub.2 (loading given) were added via the septum to the vial. The vial was placed in an argon containing autoclave and the autoclave was flushed with argon (10 min). The autoclave was pressurized with hydrogen gas (10 bar) and subsequently depressurized to atmospheric pressure three times. After this the autoclave was pressurized to 60 bar hydrogen pressure and was placed in a suitable alumina block. After heating to 85° C. the reaction was kept at this temperature for 3 h. After cooling to room temperature and depressurizing, the vial was taken out of the autoclave and the reactions outcome was determined by GC-FID analysis (deluted with EtOH) and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE-US-00006 TABLE 5 BF.sub.3*OEt.sub.2 Conversion Example (mol %) GC (% a/a) 55 — <1 56 1 86 57 3 88 58 5 82

Examples 59 and 60

[0386] Iridium catalyst (1) from DE112015001290 T5 is an example of the catalyst structures of formula (IXb). Also using this catalyst the presence of BF.sub.3*OEt.sub.2 has a strong influence on conversion and a slightly positive influence on ee (General conditions: 0.2 mol % catalyst (I) from DE112015001290 T5, 40° C., 30 bar H.sub.2, starting material concentration 0.1 M in trifluoroethanol)

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TABLE-US-00007 TABLE 5 Reaction Conv. ee Example Additive time [%] [%] Example 59-1 —  4 h 33 79 Example 59-2 — 16 h 35 79 Example 60-1 1 mol %  4 h 75 83 BF.sub.3*OEt.sub.2 Example 60-2 1 mol % 16 h 80 82 BF.sub.3*OEt.sub.2