Design of Iridium N-Heterocyclic Carbene Amino Acid Catalysts for Asymmetric Transfer Hydrogenation of Aryl Ketones

A series of chiral complexes of the form Ir(NHC)(2)(aa)(H)(X) (NHC = N-heterocyclic carbene, aa = chelated amino acid, X = halide) was synthesized by oxidative addition of alpha-amino acids to iridium(I) bis-NHC compounds and screened for asymmetric transfer hydrogenation of ketones. Following optimization of the reaction conditions, NHC, and amino acid ligands, high enantioselectivity was achieved when employing the Ir(IMe)(2)(l-Pro)(H)(I) catalyst (IMe = 1,3-dimethylimidazol-2-ylidene), which asymmetrically reduces a range of acetophenone derivatives in up to 95% enantiomeric excess.

Automated summary

A series of chiral complexes were synthesized and screened for asymmetric transfer hydrogenation of ketones, achieving high enantioselectivity with the Ir(IMe)(2)(l-Pro)(H)(I) catalyst. This catalyst asymmetrically reduces a range of acetophenone derivatives with up to 95% enantiomeric excess.