Explorations of Cascading Michael Additions
Young, Douglas M.
MetadataShow full item record
Young, Douglas M.
Intramolecular cascading Michael additions have the ability to transform simple, symmetric substrates into densely functionalized compounds containing new ring structures and chiral centers. The Rauhut-Currier (RC) reaction, also known as the vinylogous Morita-Baylis-Hillman reaction, utilizes this type of reactivity by cyclizing tethered, activated alkenes using phosphine or thiolate catalysis. This dissertation describes the expansion of the scope of the RC reaction, the introduction and importance of co-catalysts to cascading Michael additions, the development of the first amine-catalyzed RC reaction, and the transformation of cyclization products into fused, polycyclic aromatic compounds. Chapter I reviews the development and applications of the Rauhut-Currier reaction. Chapter II describes the regioselective synthesis of di-substituted indenes and introduces phenol as a rate- and selectivity-enhancing co-catalyst. Although tertiary amine nucleophiles were found to be inferior to phosphines as cyclization catalysts, chapter III discusses the ability of unhindered primary and secondary amines to undergo a diastereoselective, cascading aza-Michael-Michael addition to yield a wide variety of amino-indanes in the presence of an acid catalyst. Recognizing the importance of protic environments and small nucleophiles, the development of the first amine-catalyzed intramolecular RC is introduced in chapter IV. Chapter V describes the conversion of methyl ketone-substituted indenes to fluorene derivatives via an intramolecular aldol reaction. Chapter VI describes the serendipitous discovery and synthesis of indenopyrylium salts. Chapter VII details the novel production of indenopyridines from di-substituted indenes. Lastly, chapter VIII provides a summary and suggests future directions for this research. This dissertation includes previously published and unpublished co-authored material.