PROCESS COMPRISING THE USE OF NEW IRIDIUM CATALYSTS FOR ENANTIOSELECTIVE HYDROGENATION OF 4-SUBSTITUTED 1,2-DIHYDROQUINOLINES

Abstract

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

##STR00001##

Claims

1. A process for preparing a compound of formula (Ia) or (Ib), ##STR00017## 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) ##STR00018## wherein the substituents R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 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 the formula (IIIa) or (IIIb), ##STR00019## wherein R.sup.6 is a group of formula ##STR00020## wherein ** denotes the bond to the 6,7-dihydro-5H-cyclopenta[b]pyridine moiety, R.sup.13 is hydrogen, methyl or ethyl, R.sup.14 is C.sub.1-C.sub.6-alkyl R.sup.7 is hydrogen, R.sup.8 is C.sub.1-C.sub.4 alkyl or phenyl, wherein the phenyl 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.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.3-C.sub.8-cycloalkyl, piperidinyl and pyridyl, or R.sup.9 and R.sup.10 together with the phosphorus atom which they are bound to form a group G.sup.1 or G.sup.2 ##STR00021## 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, or R.sup.9 and R.sup.10 together with the phosphorus atom which they are bound to form a group G.sup.3 ##STR00022## in which the bonds identified by “u” and “v” are both bound directly to the phosphorus atom.

2. 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, R.sup.6 is a group of formula ##STR00023## wherein ** denotes the bond to the 6,7-dihydro-5H-cyclopenta[b]pyridine moiety, R.sup.13 is hydrogen, methyl or ethyl, R.sup.14 is C.sub.1-C.sub.4-alkyl R.sup.7 is hydrogen, R.sup.8 is C.sub.1-C.sub.4 alkyl or phenyl, wherein the phenyl is unsubstituted or substituted by one to five C.sub.1-C.sub.4-alkyl substituents, R.sup.9 and R.sup.10 are independently from one another selected from the group consisting of iso-propyl, tert-butyl, cyclopentyl, cyclohexyl and piperidin-1-yl.

3. 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 2,6-diethyl-4-methylphenyl, R.sup.7 is hydrogen, R.sup.8 is methyl, R.sup.9 and R.sup.10 are independently from one another selected from the group consisting of cyclohexyl and piperidin-1-yl.

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, 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 C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, 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 and C.sub.1-C.sub.6-alkyl.

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, R.sup.6 is 2,6-diethyl-4-methylphenyl, R.sup.7 is hydrogen, R.sup.8 is methyl, R.sup.9 and R.sup.10 are both cyclohexyl.

6. The process according to claim 1, wherein the chiral iridium catalysts are of formulae (Va) or (Vb) ##STR00024## wherein R.sup.6 is 2,6-diethyl-4-methylphenyl, R.sup.7 is hydrogen, R.sup.8 is methyl R.sup.9 and R.sup.10 are both cyclohexyl Y is a non-coordinating anion selected from the group consisting of [B(R.sup.18).sub.4].sup.− and [Al{OC(CF.sub.3).sub.3}.sub.4].sup.− of formula (VII), wherein R.sup.18 is 3,5-bis(trifluoromethyl)phenyl.

7. The process according to claim 1, wherein the chiral iridium catalyst is of formula (Va) ##STR00025## wherein R.sup.6 is 2,4,6-trimethylphenyl, R.sup.7 is hydrogen, R.sup.8 is methyl R.sup.9 and R.sup.10 are both cyclohexyl Y is [Al{OC(CF.sub.3).sub.3}.sub.4].sup.− of formula (VII).

8. The process according to claim 1, wherein the process is performed in presence of an additive, which is selected from the group consisting of Brønsted acids, Lewis acids, and mixtures thereof.

9. The process according to claim 8, 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 (Ill) trifluoromethanesulfonate, scandium (Ill) trifluoromethane-sulfonate, aluminum (Ill) fluoride, titanium (IV) isopropoxide, trimethyl aluminum, boron trifluoride, complexes of boron trifluoride, and mixtures thereof.

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

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

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

13. The process according to claim 1, wherein the amount of additive used is within the range of from 0.1 mol % to 10 mol %.

Description

EXAMPLES

[0187] 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.

Examples 1-12

[0188] The Ir-complex (catalyst loading given) and 0.64 g 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol) 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) was 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 (diluted with EtOH) and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE-US-00003 TABLE 2 catalyst Reaction loading Conversion Enantiomeric Example Catalyst time (h) (mol %) GC (% a/a) excess (% ee) 1 Va-6 3 0.02 78.8 98.8 2 Va-11 3 0.02 85.2 98.8 3 Va-4 3 0.02 <1 — 4 Va-5 3 0.02 58 n.d. 5 Va-7 3 0.02 <1 — 6 Va-8 3 0.02 2 — 7 Va-3 3 0.02 37.5 n.d. 8 Va-1 16 0.025 98.2 96.2 9 Va-1 6 0.03 94.9 n.d. 10 Va-2 6 0.03 96.1 n.d. 11 Va-9 16 0.03 81.3 n.d. 12 Va-12 16 0.03 79.4 n.d.

Examples 13-18

[0189] The Ir-complex (catalyst loading given) and 2.56 g 1-(2,2,4-trimethyl-1-quinolyl)ethanone (12 mmol) were placed in an 25-mL autoclave. The autoclave was flushed with argon (10 min). Hexafluoroisopropanol (HFIP, 16 mL) was 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 (diluted with EtOH) and the enantiomeric excess by HPLC analysis.

TABLE-US-00004 TABLE 3 catalyst Reaction loading Conversion Example Catalyst time (h) (mol %) GC (% a/a) 13 Va-10 17 0.01 82.5 14 Va-10 40 0.01 93.9 15 Va-1 17 0.01 93.1 16 Va-1 40 0.01 98.0 17 Va-1 6 0.01 50.8 18 Va-2 6 0.01 53.4

Examples 19-48

[0190] The Ir-complex Va-1 (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 mi). 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 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 (diluted with EtOH) and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE-US-00005 TABLE 4 catalyst Additive Reaction loading Conversion Enantiomeric Example (mol %) time (h) (mol %) GC (% a/a) excess (% ee) 19 — 16 0.02 95.3 n.d. 20 — 21 0.02 95.5 n.d. 21 — 3 0.02 55.2 n.d. 22 — 16 0.03 97.6 n.d. 23 Pentafluorophenol (1) 16 0.02 97.2 n.d. 24 1,2,2,6,6-Pentamethylpiperidin (1) 16 0.02 67.1 n.d. 25 Nonafluoro-tert-butyl alcohol (1) 16 0.03 96.3 n.d. 26 Nonafluoro-tert-butyl alcohol (5) 16 0.03 97.5 n.d. 27 3,5-bis-trifluorophenol (1) 16 0.02 95.7 n.d. 28 AcOH (1) 16 0.02 96 n.d. 29 AcOH (5) 3 0.02 66.5 n.d. 30 AcOH (10) 3 0.02 63.7 n.d. 31 AcOH (20) 3 0.02 54.2 n.d. 32 HPF.sub.6 (1) 3 0.02 >99 n.d. 33 HBF.sub.4*OEt.sub.2 (1) 16 0.02 90.5 n.d. 34 TfOH (1) 16 0.02 76.9 n.d. 35 Sc(OTf).sub.3 (1) 3 0.02 >99 99 36 BF.sub.3*OEt.sub.2 (1) 3 0.02 98.9 98 37 BH.sub.3*THF (1) 3 0.02 69.8 n.d. 38 BF.sub.3*AcOH (1) 3 0.02 >99 n.d. 39 BF.sub.3*n-PrOH (1) 3 0.02 >99 n.d. 40 Al(OTf).sub.3 (1) 3 0.02 >99 n.d. 41 AlF.sub.3 (1) 3 0.02 65.9 n.d. 42 AlMe.sub.3 (1) 3 0.02 91.1 n.d. 43 Ti(O.sup.iPr).sub.4 (1) 3 0.02 90.7 n.d. 44 BPh.sub.3 (1) 3 0.02 85.4 n.d. 45 B(C.sub.6F.sub.5).sub.3 (1) 3 0.02 >99 .sup. 97.6 46 B(C.sub.6F.sub.5).sub.3 (0.5) 3 0.02 97.3 n.d. 47 B(C.sub.6F.sub.5).sub.3 (0.1) 3 0.02 63.3 n.d. 48 B(OH).sub.3 (1) 3 0.02 72.7 n.d.

Examples 49-54

[0191] The Ir-complex Va-1 (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 (diluted with EtOH) and the enantiomeric excess by HPLC analysis.

TABLE-US-00006 TABLE 5 catalyst Additive Scale (amount of Reaction loading Conversion Enantiomeric Example (mol %) compound (II)) time (h) (mol %) GC (% a/a) excess (% ee) 49 — 9 mmol 6 0.01 50.8 n.d. 50 B(C.sub.6F.sub.5).sub.3 (0.5) 9 mmol 20 0.01 85.2 n.d. 51 BF.sub.3*OEt.sub.2 (1) 10 mmol  16 0.01 99.2 n.d. 52 Al(OTf).sub.3 (1) 10 mmol  16 0.01 >99 n.d. 53 HPF.sub.6 (1) 9 mmol 16 0.01 97.3 n.d. 54 BF.sub.3*AcOH (1) 9 mmol 16 0.01 98.1 n.d.

Examples 55-56

[0192] 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 (diluted with EtOH) and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE-US-00007 TABLE 6 catalyst Additive Reaction loading Conversion Enantiomeric Example Catalyst (mol %) time (h) (mol %) GC (% a/a) excess (% ee) 55 Va-6 — 3 0.02 78.8 98.8 56 Va-6 BF.sub.3*OEt.sub.2 (1) 3 0.02 94.2 99

Examples 57-60

[0193] The Ir-complex Va-1 (0.02 mol %, 0.6 μmol) 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 (IFE, 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 (diluted with EtOH) and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE-US-00008 TABLE 7 BF.sub.3*OEt.sub.2 Conversion Example (mol %) GC (% a/a) 57 — <1 58 1 86 59 3 88 60 5 82

COMPARATIVE EXAMPLES

[0194] The Ir-complex (catalyst loading given) and 0.64 g 1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol) 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) was 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 (diluted with EtOH) and the enantiomeric excess by HPLC analysis.

TABLE-US-00009 TABLE 8 Catalyst loading Example Catalyst (mol %) Time (h) Conversion 17 Va-1 0.01 6 50.8 18 Va-2 0.01 6 53.4 15 Va-1 0.01 17 93.1 13 Va-10 0.01 17 82.5 61 Va-10 0.025 16.5 98 62 Va-13 0.1 16 99.2 63 Ir catalyst (1) 0.1 16 84

[0195] This collection of experimental results shows the superiority of complexes Va-1 and Va-2. Va-2 performs gives slightly higher conversion than Va-1 after 6 h with 0.01 mol % of catalyst. Va-1 gives significantly higher conversion than Va-10 (=Va-10 from WO2019/185541 A1) after 17 h with 0.01 mol % of catalyst. Va-10 gives similar performance than Va-13 (=Va-1 from WO2019/185541 A1) although only ¼ of the catalyst amount was used. It must thus be considered superior to Va-13. Va-13 gives superior conversion compared to Ir catalyst (I) from DE112015001290 T5. Moreover, all of the catalyst Va gives superior enantioselectivities (>95% ee) compared to Ir catalyst (1) from DE112015001290 T5 (81.7% ee). Catalyst Va-1 gives higher conversion (93.1 vs 84%) than Ir catalyst (1) from DE112015001290 T5 even at only one-tenths of the catalyst loading (0.01 vs 0.1 mol %).

##STR00016##