Lithium chloride-mediated stereoselective synthesis of cyclopropanecarboxamides from γ,δ-epoxy malonates through a domino cyclopropanation/lactonization/aminolysis process.
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.
Departamento de Química, Universidade Federal de Santa Catarina , Florianópolis, Santa Catarina 88040-900, Brazil.
Marcelo V
MV
Marques
Marcus M
MM
Sá
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D058116:Lewis Acids / Q000737:chemistry*; D018021:Lithium Chloride / Q000737:chemistry*; D008314:Malonates / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000577:Amides; D000588:Amines; D003521:Cyclopropanes; D007783:Lactones; D058116:Lewis Acids; D008314:Malonates; D018021:Lithium Chloride; C538819:cyclopropanecarboxamide