Enhancement of neighbouring-group participation in Cu0-promoted cross-coupling gem-difluoromethylenation of aryl/alkenyl halides with 1,3-azolic difluoromethyl bromides.
Chemistry
; 20(32): 10084-92, 2014 Aug 04.
Article
em En
| MEDLINE
| ID: mdl-24990326
ABSTRACT
A copper(0)-promoted direct reductive gem-difluoromethylenation of unactivated aryl or alkenyl halides with benzo-1,3-azolic (oxa-, thia- or aza-) difluoromethyl bromides or 2-bromodifluoromethyl-1,3-oxazoline has been developed for the construction of pharmaceutically important gem-difluoromethylene-linked twin molecules. The unique π-conjugated aryl-fused 1,3-azolic moiety in difluoromethyl bromide substrates could stabilise the reaction intermediates, which promotes the reactivities, providing facile access to the cross-coupling products in good to excellent yields, and allowing significant functional group tolerance. The reaction exhibits an enhanced neighbouring-group-participation effect. This method could provide a new strategy for the construction of gem-difluoromethylene-linked identical or nonidentical twin drugs through further functionalisation of 1,3-azolic skeletons.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxazóis
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Derivados de Benzeno
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Brometos
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Cobre
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Alcenos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article