A Practical 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.