Enantioselective Michael addition of malononitrile to chalcone with bifunctional squaramide organocatalysts

Sargın, Nurdan
4H-pyran derivatives show diverse biological activity such as antimicrobial, antibacterial, antiviral and antifungal. 4H-pyran derivatives can be synthesized easily from 2-(3-oxo-1,3-diphenylpropyl)malononitrile which is the Michael addition product of malononitrile to trans-chalcone. Synthesizing chiral biologically active compounds with metal free approach (organocatalysis) is a significant topic. In this thesis, chiral 2-(3-oxo-1,3-diphenylpropyl)malononitrile was synthesized with quinine or 2-aminoDMAP based novel bifunctional organocatalysts which were developed in our group. In the asymmetric Michael addition reaction, 2-adamantyl anchored quinine-squaramide organocatalyst was found the best among the other tested organocatalysts in the optimization reactions. Consequently, 10 different derivatives of Michael product were synthesized up to 86% ee under the optimized condition with very low catalyst loading (0.5 mol%).