Asymmetric transfer hydrogenation of aromatic ketones and azirines with NH-ligands

The Ru(arene)[(1 S , 3 R , 4 R )-3-(Hydroxymethyl)-2-azabicyclo[2.2.1]heptane catalyst was optimized as ligand in the asymmetric transfer hydrogenation of ketones and resulted in increased activity and enantioselectivity of the catalyst. Dioxolane substitution at the rear end of the amino alcohol ligand and introduction of a ( R )-methyl substituent yielded a catalyst that reduced acetophenone in 96% enantiomeric excess in 90 minutes with a substrate to catalyst molar ratio of 5000. A diversity of substituted aromatic ketones was reduced with excellent rate and enantioselectivity. Based on experimental and computational results, a study of the origin of the enantioselectivity was conducted. A combination of electrostatic, steric, dispersion forces and solvation effects was suggested to be the cause of the stereo discrimination. A set of amino sulfides built upon the 2-azabicyclo and the cyclohexane structures were prepared and tested as ligands in the enantioselective transfer hydrogenation of acetophenone with [IrCl(COD)] 2 as metal precursor. With this type of catalysts, the reaction rates were good but the enantioselectivity unsatisfactory with 70% as the highest obtained enantiomeric excess. The first enantioselective reduction of aromatic 2 H -azirines was accomplished by using the asymmetric transfer hydrogenation protocol. Aromatic azirines were reduced to yield chiral aziridines with up to 72% enantiomeric excess and good yields. The enantioselectivity and reactivity of the reaction were strongly influenced by substituents on the aromatic and aliphatic moiety of the substrate.