C-H Functionalization of Pyridines via Oxazino Pyridine Intermediates: Switching to para-Selectivity under Acidic Conditions.
J Am Chem Soc
; 145(28): 15581-15588, 2023 Jul 19.
Article
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| MEDLINE
| ID: mdl-37428649
ABSTRACT
para-Selective C-H functionalization of pyridines holds a significant value but remains underdeveloped. Site-switchable C-H functionalization of pyridines under easily tunable conditions expedites drug development. We recently reported a redox-neutral dearomatization-rearomatization strategy for meta-C-H functionalization of pyridines via oxazino pyridine intermediates. Here, we demonstrate that these oxazino pyridine intermediates undergo highly para-selective functionalization simply by switching to acidic conditions. A broad scope of para-alkylated and arylated pyridines is prepared through radical as well as ionic pathways. These mild and catalyst-free methods are applied to the late-stage para-functionalization of drugs using pyridines as the limiting reagents. Consecutive meta,para-difunctionalization of pyridines is also achieved with complete regiocontrol relying on the pH-dependent reactivity of oxazino pyridines.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
J Am Chem Soc
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania