Thesis advisor: Jeffrey A. Byers / Chapter 1: There are a limited number of examples of metal-catalyzed Brook rearrangements in the literature, none of which involve ruthenium, rhodium, or iridium which are common ketone hydrogenation catalysts. The content of this chapter introduces the traditional Brook rearrangement and its advantages and disadvantages in chemical synthesis. Furthermore, the few examples of metal-catalyzed Brook rearrangements of acylsilanes and structurally similar moieties are discussed. Chapter 2: Utilizing a Brook rearrangement under hydrogenation or transfer hydrogenation conditions opens up a new area of catalytic reactivity that has not been fully explored. To our knowledge, metal complexes based on ruthenium and rhodium have never been shown to catalyze a Brook rearrangement of acylsilanes. This chapter describes the mechanistic implications of a Brook rearrangement under hydrogenation or transfer hydrogenation conditions as well as the first example of a ruthenium-catalyzed Brook rearrangement of aryl acylsilanes. Chapter 3: Pioneering work performed by Jeffrey Johnson and co-workers in the area of catalytic coupling of acylsilanes and various electrophiles showed that formation of new C-C bonds through a Brook rearrangement can be a powerful synthetic tool. In this chapter, we investigate an intermolecular coupling of aryl acylsilanes and aldehydes through a metal-catalyzed Brook rearrangement under transfer hydrogenation conditions to yield two synthetically useful motifs, specifically oxygenated bicyclic compounds. A reaction screen was performed on the coupling capabilities of these two species with various ruthenium and rhodium catalysts. The result of the screen was synthesis of a silyl ether acetal through employing the starting material as the reducing equivalent. Additionally, mechanistic insight was gained to further develop the proposed methodology. Chapter 4: An intramolecular approach to achieving coupling of acylsilanes and many different types of electrophiles was envisioned as a way of furnishing synthetically useful bicyclic compounds in one step. The focus of this chapter is the synthesis of a novel acylsilane that we proposed could undergo an intramolecular cross coupling reaction under transfer hydrogenation conditions. The conclusion of this chapter outlines the future direction of the project, which entails a new route to an intermolecular cross coupling of acylsilanes and various electrophiles. Published work from Michael Krische's laboratory helped us envision a different type of acylsilane, specifically an α,β-unsaturated acylsilane, in which binding to a metal center would proceed through a π-allyl intermediate. Ongoing efforts in the coupling of α,β-unsaturated acylsilanes with electrophiles are currently underway. / Thesis (MS) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

La thèse est divisée en trois chapitres indépendants. Chimie du β-lactames : Synthèse d'α-éthylène et d'α-alkylidène-β-lactames en utilisant la réaction de Kinugasa. Chimie de l'acylsilane : application d'une réaction aldolique intramoléculaire asymétrique sur un dérivé d'acylsilane nouvellement synthétisé. - Chimie médicinale: synthèse de nouvelles molécules à but anticancéreux.Dans le premier chapitre la réaction de Kinugasa a été appliquée pour la première fois à des alcynes vrais, portant en position propargylique un groupe partant permettait d'accéder directement et en une étape aux méthylène- et alkylidene β-lactames recherchés. Dans le second chapitre, la synthèse de molécules originales possédant à la fois une fonction acylsilane et un aldéhyde en position éloignée, et l'aldolisation intramoléculaire asymétrique a été explorée. Dans le dernier chapitre, notre objectif était de restaurer les propriétés apoptotiques au sein des cellules cancéreuses afin d'obtenir de nouveaux composés à activité antitumorale. A partir de données obtenues par modélisation moléculaire, nous avons fait le design de plusieurs séries d'analogues d'un inhibiteur connu(MIM-1) de la protéine anti-apoptotique Mcl-1. Huit composés ont été synthétisés et testés pour trois types de cellules cancéreuses (sein, ovaire et le mélanome). / The thesis is divided into three chapters:- β-lactams chemistry: synthesis of α-methylene and α-alkylidene-β-lactams using the Kinugasa reaction.- Acylsilane chemistry : applying asymmetric intramolecular aldol reaction on a newly synthesized acylsilane derivatives. - Medicinal chemistry: synthesis of new molecules with anticancer aimes. In the first chapter, Kinugasa reaction was applied for the first time with an alkyne bearing a nucleofuge in propargylic position that allowed us to discover a way of synthesis of exoalkylidene β-lactams. In the second chapter, a new acylislane derivatives bearing an aldehyde functional group in a remote position of the molecule were prepared, and asymmetric intramolecular aldolization reaction was performed. In the last chapter, our goal was to reinduce the pro-apoptotic properties in cancer cells in order to obtain new antitumor compounds. Starting from data obtained through molecular modeling studies, we designed and prepared several series of analogs for a known inhibitor (MIM-1) of the anti-apoptotic protein Mcl-1. Eight compounds have been synthetized and screened towards three types of cancer cells (breast, ovarian and melanoma).