1,5,7-Triazabicyclo[4.4.0]dec-5-ene: An Effective Catalyst for Amide Formation by Lactone Aminolysis

The amide is one of the most prevalent functional groups throughout natural and engineered chemical space. Among various methods of constructing amide bonds, lactone aminolysis remains one of the most atom economical. Herein, we report 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as an effective catalyst for lactone aminolysis under mild conditions. This methodology is compatible with a wide range of lactones and amines (>50 examples), including various natural products and pharmaceuticals, and applicable to the synthesis of bioactive molecules. Detailed mechanistic studies under synthetically relevant conditions, including reaction progress kinetic analysis and variable time normalization analysis, reveal a likely mechanism for this reaction involving acyl-TBD as the reactive intermediate.