A Homogeneous Nickel Catalyst for Reductive Amination of γ-Keto Acids using Hydrogen

Abstract

The reductive amination of levulinic and 2-acetyl benzoic acids with hydrogen and various amines proceeds efficiently in the presence of a homogeneous Ni/triphos-catalyst. The reaction rate of the overall process is significantly enhanced using 3,3,3-trifluoroethanol (TFE) as solvent. The optimized synthetic protocol allows for a straightforward access of >20 examples of N-functionalized pyrrolidinones in high yields (75 % and >99 %). Upscaling to 10 mmol-scale is demonstrated and mechanistic in situ studies revealed the presence of alkoxy- and hydroxylactams as crucial intermediates. Show more