Metal‐Free Synthesis of N‐Aryl Amides using Organocatalytic Ring‐Opening Aminolysis of Lactones

Catalytic ring‐opening of bio‐sourced non‐strained lactones with aromatic amines can offer a straightforward, 100 % atom‐economical, and sustainable pathway towards relevant N‐aryl amide scaffolds. Herein, the first general, metal‐free, and highly efficient N‐aryl amide formation is reported from poorly reactive aromatic amines and non‐strained lactones under mild operating conditions using an organic bicyclic guanidine catalyst. This protocol has high application potential as exemplified by the formal syntheses of drug‐relevant molecules. Green Amides: A general, metal‐free organocatalytic process for N‐aryl amide synthesis has been developed using cheap and readily available lactones and aromatic amines. The formal ring‐opening aminolysis (ROA) of the lactone partner occurs under mild reaction conditions and highlights the use of potentially bio‐sourced lactones. The formal synthesis of pharma‐relevant suberoyl‐anilide‐hydroxamic acid (SAHA) compounds is demonstrated using this new ROA methodology.