xx, 214 p. : ill. (some col.) / 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 This dissertation includes previously published and unpublished co-authored material. / Committee in charge: Shih-Yuan Liu, Chairperson; Kenneth Doxsee, Advisor; David Tyler, Member; Michael Haley, Member; A. Dana Johnston, Outside Member

La nécessité grandissante de disposer d’une large librairie de diverses petites molécules pour le screening biologique constitue une puissante force motrice pour les chimistes organiciens et requiert en amont le développement de méthodologies rapides et efficaces. Dans ce cadre, nous nous sommes plus particulièrement intéressés à la fonctionnalisation d’énamides qui représentent des blocs moléculaires intéressants permettant d’introduire des fonctionnalités aminées dans des systèmes variés. Notre objectif a été de synthétiser des petites bibliothèques de molécules azotées à partir de substrats communs tout en mettant en oeuvre les différentes stratégies de la synthèse orientée vers la diversité et en s’attachant à respecter les règles suivantes : économie d’atomes, processus catalysés, synthèses rapides en peu d’étapes et contrôle de la stéréoselectivité. Dans un premier temps, nous avons principalement synthétisé divers énamides, nous permettant par la suite de développer des méthodologies innovantes et d’accéder à des « structures privilégiées » ou des fragments clés présents dans des produits naturels ou dans des substances potentiellement biologiquement actives en mettant en jeu des processus variés telles que des réactions d’aza-Michael, d’oxyamidation ou en cascade et la chimie du palladium avec de la CH insertion, des dioxoazoborocanes ou encore l’utilisation de l’auxiliaire chiral SAMP. / The continuing demand to synthesize new and original collections of small molecules for the biological screening is an attractive subject for organic chemists and requires upstream the development of fast and easy synthetic methods. In this context, we decided to focus particularly on the functionalization of enamides which represent valuable building blocks in order to introduce nitrogen based functionality into various organic systems. Our objective was to synthesize new nitrogen containing compound libraries starting from common substrates by applying Diversity-Oriented Synthesis strategy and following these rules: atom economy, catalyzed reactions, fast synthesis in few steps and control of stereoselectivity. Firstly we mainly synthesized enamides. Thereafter, we developped efficient methodologies giving access to motifs frequently found in “privileged structures” or key scaffolds present in natural products or potential bioactive compounds thanks to various processes like aza-Michael, oxyamidation or cascade reactions, palladium chemistry with CH activation, dioxoazoborocanes or chiral auxiliary SAMP.