Asymmetric Organocatalyzed Cyclization Reactions

The aim of this project is to develop new asymmetric organocatalytic versions of cyclization reactions using secondary amine-catalysis. The most recent organocatalytic concepts are based on one-pot, tandem and domino reactions. With these cascade reactions, complex chiral molecules can be obtained, which are often valuable building blocks in the total synthesis of natural products. Various metal-based stereoselective cyclization protocols have been established within the last decades, but recently the development of analogous organocatalytic methods has become an important challenge. This project will contribute to this new task by developing organocatalytic versions of the following reactions: Danheiser annulation Nazarov cyclization homo-Nazarov cyclization The Danheiser annulation is originally a TiCl 4 -promoted reaction of an alpha,beta-unsaturated carbonyl compound and an allenylsilane to form five-membered rings. It is envisaged to develop the first asymmetric organocatalyzed Danheiser reaction in this project, using chiral secondary amine catalysts. Thereby mono- and bicyclic structures, as well as spiro-fused compounds should be synthesized using this method. The Nazarov cyclization is an electrocyclic reaction, that allows the formation of five-membered rings from dienones. Here, a stereoselective and metal-free variant using iminium-ion catalysis will be developed. Finally, the homo-Nazarov reaction will be studied. In this transformation, vinyl- cyclopropyl ketones are cyclized to form six-membered rings via a carbocation formation. An enantioselective organocatalytic version of this reaction would allow the preparation of chiral substituted cyclohexenones. Additionally, a consecutive functionalization of the alpha,beta-unsaturated carbonyl moiety in the cyclohexenone would give access to even higher substituted six-membered rings.