Nitrogen heterocycles are present in nearly 60% of all small-molecule drugs approved by the US Food and Drug Administration. New innovative methods that streamline the synthesis of such heterocycles are therefore highly desirable. The use of new or underdeveloped reactive intermediates provides an excellent opportunity to develop novel heterocyclic syntheses. For example, nitrogen-substituted isocyanates (N-isocyanates) are a class of rare amphoteric isocyanates with high, but severely underdeveloped synthetic potential. The research efforts presented in this thesis have been directed towards the use of such intermediates for the rapid construction of heterocycles using cascade reactions. Using an in situ generation approach from masked (blocked) isocyanate precursors, we were able to control the homo dimerization of these species and design several cascade reactions forming more than 10 different classes of heterocycles using appropriate nitrogen nucleophiles. Given the importance of the N-N-C=O motif in pharmaceuticals and agrochemicals, N-isocyanates provide the opportunity to synthesize highly desirable cores for different industrial applications. To illustrate the potential of this new tool in heterocyclic chemistry, more than 200 heterocycles were synthesized using this methodology. In Chapter 2, heterocycles incorporating only one atom from the N-isocyanate will be presented. More precisely, the first cascade reaction involving N-isocyanates for the rapid synthesis of saturated heterocycles will be presented. The incorporation of 2 atoms within the ring will then be discussed in Chapter 3 with the synthesis of hydantoins, imidazolones, thiazolines, pyrazoles and phthalazinones. Chapter 4 will focus on the incorporation of every atom in the heterocycle to form other bioactive cores such as azauracils, pyridazinones and azadiketopiperazines. Lastly, Chapter 5 will describe our efforts for the synthesis of acyclic molecules such as semicarbazides and aza-peptides.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Metal-catalyzed cycloadditions of alkynes with isocyanates or nitriles are valuable tools for the synthesis of complex carbocycles and heterocycles. Although this transformation has been studied for over three decades, the cyclizations of disocyanates with 1,3-dienes or allenes are not known and the asymmetric cycloadditions of isocyanates are scarce. To expand the scope of these powerful reactions, we studied the semi-intramolecular metal-catalyzed cycloaddition of several unsaturated systems with isocyanates. Our results show that further work in this area is needed to suppress the formation of undesired homo-coupled adducts and obtain the bicyclic products in a more efficient manner. 1,3-butadienes are versatile building blocks in organic synthesis. Therefore, it is our interest to develop an efficient method for their preparation making 1,3-butadienes more available for the organic chemist. A number of methods are known for the synthesis of these compounds, but the majority of them present problems such as poor regioselectivity, low atom economy, or require the use of toxic or non-readily available reagents. In order to develop a more effective synthesis, we employed (allenylmethyl)silanes as intermediates for the preparation of 1,3-butadienes utilizing (4-bromobut 2-ynyl)trimethylsilane as a diene equivalent. A Nozaki-Hiyama-Kishi type transformation was used for the highly regioselective preparation of (trimethylsilyl)methylallenic alcohols from aldehydes and ketones. In addition, several tridentate bis(oxazolinyl)carbazole ligands were synthesized and used for the enantioselective synthesis of allenic alcohols. Carbazole ligands synthesis was achieved by the Suzuki coupling of carbazoles with different boronic acids followed by carbonylative amidation and cyclization. We report an efficient new method for the desilylation of allenic alcohols providing a variety of secondary and tertiary 1,3-butadienylcarbinols. Furthermore, our interest in extending this methodology led us to the discovery of a novel synthesis of 2-aminomethyl-1,3-dienes from N-tosyl imines.

Thesis (Ph. D.)--University of Missouri-Columbia, 1995. / Typescript. Vita. Includes bibliographical references (leaves 108-117). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1995. / Typescript. Vita. Includes bibliographical references (leaves 108-117). Also available on the Internet.

Thèse doctorat : Matériaux Polymères et Composites : Villeurbanne, INSA : 2005. / Titre provenant de l'écran-titre. Bibliogr. p. 197-206. Réf. bibliogr. p. 227-228.

Thèse de doctorat : Chimie organique : Lille 1 : 2002. / N° d'ordre (Lille) : 3249. Résumé en français et en anglais. Bibliogr. en fin de chapitres. Glossaire.

Thesis (Ph. D.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains xvi, 377 p. : ill. Includes abstract. Includes bibliographical references (p. 120-128).

Thèse (M.Sc.)--Université Laval, 2002. / Bibliogr.: f. [123]-131. Publié aussi en version électronique.