Enantioselective hydrogenation of 4-substituted 1,2-dihydroquinolines in presence of a chiral iridium catalyst and an additive

A process for preparing a compound of formula (Ia) or (Ib),

• wherein
• R1 is C1-C6-alkyl,
• R2 and R3 are the same and are selected from C1-C4 alkyl,
• R4 is C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenyl or benzyl,
• n is 0, 1, or 2,
• each substituent R5, if present, is independently selected from the group consisting of halogen, C1-C6-alkyl, and C1-C6-haloalkyl,
• comprising enantioselective hydrogenation of a compound of formula (II)
• wherein the substituents R1, R2, R3, R4, R5 and the integer n are each as defined for the compound of formula (Ia) or (Ib),
• in presence of a chiral iridium catalyst, wherein
• the chiral iridium catalyst comprises a chiral ligand of formula (IIIa), (IIIb), (IXa) or (IXb),
• wherein
• R6 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, C1-C4-alkoxy, C1-C4-alkyl, C1-C4-haloalkyl and phenyl, wherein the phenyl is unsubstituted or substituted by one to five C1-C6-alkyl substituents,
• R7 and R8 are independently from one another hydrogen or C1-C6-alkyl,
• R9 and R10 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,
• R19 is phenyl or t-butyl,
• R20 is hydrogen or methyl,
• each R21 is independently selected from benzyl and methyl,
• each R22 is cyclohexyl,
• and
• in the presence of an additive,
• 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-pentafluoro-phenyl)borane, aluminum (III) trifluoromethanesulfonate, scandium (III) trifluoromethanesulfonate, aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum, boron trifluoride, boron trifluoride diethylether, boron trifluoride acetic acid and boron trifluoride n-propanol, and mixtures thereof.