| Institution: | 1. Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016 India
These authors contributed equally to this work.;2. Department of Chemistry, National Institute of Technology Manipur, Langol, Imphal West, 795004 India;3. Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016 India |
| Abstract: | 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. |
