Asymmetric Organocatalytic Synthesis of Substituted Chiral 1,4‑Dihydropyridine Derivatives

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.