Asymmetric Organocatalytic Synthesis of Substituted Chiral 1,4-Dihydropyridine Derivatives
Fernando Auria-Luna1, Eugenia Marqués-López1, M Concepción Gimeno1
1Laboratorio de Organocatálisis Asimétrica, Departamento de Química Orgánica, ‡Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza , C/Pedro Cerbuna, 12, E-50009, Zaragoza, Spain.
Abstract:
The first cinchona-alkaloid-organocatalyzed enantioselective synthesis of chiral 1,4-dihydropyridine derivatives is described. Bis-cinchona catalyst 3b activates the Michael addition reaction between malononitrile derivatives 2 and enamines 1, affording the appealing and highly substituted 1,4-dihydropyridines 4 with very good results in most cases. This is one of very few examples of the synthesis of chiral 1,4-dihydropyridines by an enantioselective catalytic procedure. The highly substituted final compounds are of interest for their potential biological activity. This efficient protocol opens the door to a new area of research for the asymmetric construction of these skeletons for which enantioselective syntheses are still very limited.
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