Intramolecular Direct Arylation of 3-Halo-2-pyrones and 2-Coumarins.
J Org Chem
; 80(21): 10904-13, 2015 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-26491882
ABSTRACT
Direct arylation represents a favorable alternative to traditional cross-coupling and has found widespread use with simple aryls and robust heterocycles. Herein a direct arylation protocol has been optimized and applied to 2-pyrones, which are delicate and privileged biological motifs. Regioselective halogenation at the 3-position allows intramolecular coupling by activation of a pyrone C-Br or C-Cl bond and a phenoxy C-H bond. Importantly, electron-poor phenoxy substrates also worked well. The methodology was extended to 2-coumarins and applied to the synthesis of flemichapparin C and a novel analogue. Deuterium isotope effects, typical of a concerted metalation-deprotonation (CMD) mechanism, were observed in the case of a bromopyrone, but a highly unusual, inverse kinetic isotope effect was evident using a chlorocoumarin, implying that a different mechanism is operating.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deutério
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Irlanda