Lithium chloride-mediated stereoselective synthesis of cyclopropanecarboxamides from γ,δ-epoxy malonates through a domino cyclopropanation/lactonization/aminolysis process.
J Org Chem
; 79(10): 4650-8, 2014 May 16.
Article
em En
| MEDLINE
| ID: mdl-24758748
ABSTRACT
The stereoselective synthesis of novel multifunctionalized cyclopropanes from γ,δ-epoxy malonates and amines mediated by LiCl under mild conditions was carried out. This domino reaction involves the initial cyclopropanation via intramolecular ring-opening of γ,δ-epoxy malonates through the cooperative catalysis of LiCl (acting as a Lewis acid) and a Brønsted base (a primary or, in selected cases, a secondary amine). The sequential events consisted of lactonization and aminolysis of the lactone ring, which ultimately furnished cyclopropanecarboxamides with different substitution patterns in good isolated yields. In all cases, a quaternary stereogenic center could be perfectly assembled, with a single diastereoisomer being obtained. This method proceeds with high atom economy, is remarkably modular and operationally simple, and tolerates a variety of functional groups. The involvement of readily available starting materials, the broad scope, and the use of a sustainable solvent (methanol or ethanol) at ambient temperature make this domino process highly effective. A reaction mechanism is proposed on the basis of the experimental observations involving the preparation and reactivity of cyclopropylidene lactones as possible intermediates of the domino process.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cloreto de Lítio
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Ciclopropanos
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Ácidos de Lewis
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Amidas
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Aminas
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Lactonas
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Malonatos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article