SB-214111

Reversing the conventional site‐selectivity of C−H activation provides efficient retrosynthetic disconnections to otherwise unreactive bonds. Described herein is the Brønsted acid‐catalyzed reaction that selectively performs meta‐amination of anisidines with aliphatic‐, heterocyclic‐ and aromatic amines in a one‐pot procedure. In addition to dramatically simplifying the synthesis of meta‐substituted anilines, our approach has the advantage of the scalability and remarkable functional group tolerance, including late‐stage functionalization of pharmaceutical compounds and natural products. The control experiments and detailed computational analysis provide insight into the reaction mechanism and the origin of meta‐selectivity. The protocol extended to the synthesis of challenging tri‐aminated arenes and successfully applied for the efficient synthesis of 5‐HT6 receptor antagonists, the anti‐psychotic drugs viz.. SB‐214111, SB‐258510, and specifically, anti‐schizophrenic drug SB‐271046.