Asymmetric hydrogenation of quinolines with recyclable and air-stable iridium catalyst systems

The iridium complex-catalyzed asymmetric hydrogenation of quinolines in a DMPEG/hexane biphasic system was studied. Catalysts with C2-symmetric ligands such as Xyl-P-Phos, Cl–MeO–BIPHEP, SYNPHOS, and DifluorPhos are highly effective for this type of reaction. Most of the catalysts tested can be retained in DMPEG (Mn = 500), and the asymmetric hydrogenation of various quinoline substrates can be carried out in DMPEG/hexane biphasic system with up to 92% ee. The catalysts and the products can be separated via simple phase separation, and the reactivity/stereoselectivity of the catalysts can be retained for at least three reaction cycles.

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(R)-1,2,3,4-Tetrahydro-2-methylquinolineC10H13NEe = 91%[α]D21=+88 (c 0.02, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

(R)-2-Ethyl-1,2,3,4-tetrahydroquinolineC11H15NEe = 92%[α]D21=+76 (c 0.02, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

(R)-1,2,3,4-Tetrahydro-2-propylquinolineC12H17NEe = 88%[α]D21=+84 (c 0.02, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

(R)-2-Butyl-1,2,3,4-tetrahydroquinolineC13H19NEe = 88%[α]D21=+78 (c 0.02, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

(R)-1,2,3,4-Tetrahydro-2-pentylquinolineC14H21NEe = 91%[α]D21=+100 (c 0.012, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

(R)-1,2,3,4-Tetrahydro-2,6-dimethylquinolineC11H15NEe = 87%[α]D21=+121 (c 0.007, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

(R)-1,2,3,4-Tetrahydro-6-dimethoxyl-2-methylquinolineC11H15NOEe = 87%[α]D21=+64 (c 0.02, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

(R)-1,2,3,4-Tetrahydro-2-phenethylquinolineC17H19NEe = 90%[α]D21=+95 (c 0.013, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

1-(((S)-1,2,3,4-Tetrahydroquinolin-2-yl)methyl)cyclohexanolC16H23NOEe = 85%[α]D21=+82 (c 0.01, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (S)

(R)-6-Fluoro-1,2,3,4-tetrahydro-2-methylquinolineC10H12FNEe = 90%[α]D21=+84 (c 0.015, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

1-((S)-1,2,3,4-Tetrahydroquinolin-2-yl)-2-methylpropan-2-olC13H19NOEe = 91%[α]D21=+82 (c 0.014, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (S)