Metal-Free Oxidative Annulation of Phenols and Amines: A General Synthesis of Benzoxazoles.
J Org Chem
; 87(14): 9112-9127, 2022 07 15.
Article
em En
| MEDLINE
| ID: mdl-35786919
ABSTRACT
The ubiquity of benzoxazoles in natural products, drugs, and functional materials has stimulated numerous efforts toward their synthesis; however, the developed methods rely on prefunctionalized substrates and lack generality. Under metal-free conditions, a highly general synthesis of benzoxazoles direct from abundant and easily available phenols and amines is developed via a modular phenol functionalization controlled by TEMPO. In the reaction, various phenols and primary amines with a broad range of functional groups are compatible, producing structurally and functionally diverse benzoxazoles (64 examples) without or with trace observation of the byproducts of phenol transformation with amines. The practical synthesis, especially for drug tafamidis, demonstrates decisive advantages in generality, selectivity, efficiency, and atom- and step-economies over traditional methods, even in the cases of low yields. Mechanistically, the radical adducts of TEMPO with ortho-cyclohexa-2,4-dien-1-one radicals rather than the well-recognized cyclohexa-3,5-diene-1,2-diones may serve as intermediates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
/
Aminas
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China