A Strategy for Metal-Free C-N Cross-Coupling and Late-Stage N-Arylation Enabled Smiles Rearrangement

N-substituted anilines and their derivatives are versatile building blocks for synthesizing pharmaceutical molecules, natural products, and functional materials. Given the significant role of biarylamine motifs in modern chemistry, the development of a mild and easily manageable protocol is highly desirable in contemporary organic synthesis. In this context, we develop a transition-metal-free C-N cross-coupling of carboxamides and sulfonamides, resulting in the synthesis of valuable biarylamines and alkylarylamines. This discovery represents an intermolecularly challenging Smiles rearrangement and introduces a novel method for synthesizing N-aryl/alkyl amines through the activation of carboxamides derived from carboxylic acids, a previously unexplored approach. The protocol showcases a broad substrate scope with various functional groups and scalability, providing access to key building blocks in medicinal chemistry and drug discovery. Furthermore, the developed protocol was successfully applied to 20 late-stage modifications of drugs and natural-product derivatives.