Ru(II) complexes of cyclohexane diamine and monodentate phosphorus ligands for asymmetric ketone hydrogenation

The incorporation of a trans-1,2-diaminocyclohexane in place of DPEN provides improvements in enantioselectivity to asymmetric ketone hydrogenation reactions using BrXuPHOS–Ru–diamine catalysts. Substrates containing halogenated aryl rings are particularly compatible with this catalyst, however, α-chlorinated ketones remain resistant to reduction under any conditions.

Figure optionsDownload as PowerPoint slide

(S)-(−)-1-PhenylethanolC8H10OEe 90%[α]D23=+48.6(c0.10CH2Cl2)Determined by chiral GC analysis

(S)-(−)-1-(3′-Trifluoromethylphenyl)ethanolC9H9F3OEe 93%[α]D20=-24.0(c0.24,MeOH)Determined by chiral GC analysis

(S)-(−)-1-(4′-Trifluoromethylphenyl)ethanolC9H9F3OEe 90%[α]D22=-22.3(c0.62,MeOH)Determined by chiral GC analysis

(S)-(−)-1-(2′-Bromophenyl)ethanolC9H9BrOEe 97%[α]D26=-54.5(c0.2,CHCl3)Determined by chiral GC analysis

(S)-(−)-1-(2′-Iodophenyl)ethanolC9H9IOEe 97%[α]D29=-41.3(c0.20,CHCl3)Determined by chiral GC analysis

(S)-(−)-1-(4′-Fluorophenyl)ethanolC8H9FOEe 93%[α]D30=-29.3(c0.22,CH3OH)Determined by chiral GC analysis

(S)-(−)-1-(4′-Chlorophenyl)ethanolC8H9ClOEe 90%[α]D29=-37.8(c0.30,ether)Determined by chiral GC analysis

(S)-(−)-1-(3′-Chlorophenyl)ethanolC8H9ClOEe 90%[α]D31=-24.1(c0.56,CHCl3)Determined by chiral GC analysis

(S)-(−)-1-(2′-Chlorophenyl)ethanolC8H9ClOEe 94%[α]D29=-32.9(c0.22,CHCl3)Determined by chiral GC analysis

(S)-(−)-1-(2′-Methylphenyl)ethanolC9H12OEe 92%[α]D24=-75.0(c0.15,EtOH)Determined by chiral GC analysis

(S)-(−)-1-(2,5-Dimethyl-3-thienyl)ethanolC8H12SOEe 92%[α]D28=-16.4(c0.30,CHCl3)Determined by chiral GC analysis