Practical Access to meta-Substituted Anilines by Amination of Quinone Imine Ketals Derived from Anisidines: Efficient Synthesis of Anti-Psychotic Drugs.
Angew Chem Int Ed Engl
; 62(21): e202301166, 2023 05 15.
Article
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| MEDLINE
| ID: mdl-36942400
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinonas
/
Compuestos de Anilina
Idioma:
En
Año:
2023
Tipo del documento:
Article