Intramolecular Rhodium-Catalyzed Ene-Cycloisomerization Reactions of Thioether and Triorganosilane containing Alkenylidenecyclopropanes: Novel Metal-Mediated β-Sulfide and β-Silyl Elimination Reactions

Abstract

The transition metal-catalyzed ene-cycloisomerization is a particularly attractive method for the construction of highly functionalized cyclic scaffolds. Furthermore, many elegant studies over the past few decades have led to the development of several unique methods for this transformation, employing a variety of transition metal-catalysts. In particular, the ene-cycloisomerization reaction provides carbo- and heterocyclic skeletons in a highly selective and atom-economical manner, thus offering an efficient strategy for the total synthesis of a number of natural products. The following thesis commences with a very brief introduction followed by two major section (Chapter 2 and 3) and a concluding chapter. Chapter 1 serves as a brief introduction and provides an overall outline for this thesis. Chapter 2 provides an introduction to the development of transition-metal-catalyzed ene-cycloisomerization reaction with an overview of the different reaction pathways (Section 2.1). This chapter is then divided into subsections (2.2-2.9), that are organized based on the nature of the transition metal-catalyzed ene-cycloisomerization reaction, which depends on the degree of saturation in the substrates. Chapter 3 commences with a review of the utility of alkylidenecyclopropanes (abbreviated thereafter as “ACPs”) in transition metal-catalyzed reactions. Section 3.2 provides an in-depth discussion of the reactivity of ACPs in these transformations, in which the behavior of these substrates with four different metal catalysts (Pd, Rh, Ru, Ni) is discussed. Section 3.3 describes our work on the development of the novel rhodium-catalyzed ene-cycloisomerization reaction of ACPs tethered to an allylic sulfide, which undergo an unprecedented β-sulfide elimination/migration to highlight the importance of the organosulfur chemistry. The subsequent section (Section 3.4) outlines the development of a nickel-catalyzed sulfide elimination/migration to provide products with two new stereogenic centers and one three-membered-ring. Section 3.5 outlines our efforts towards the rhodium catalyzed β-silyl elimination/migration. A detailed optimization and scope of this transformation is described, along with mechanistic studies. Finally, Chapter 4 provides a conclusion and overview of the methodologies described in this thesis and their synthetic application, especially in the synthesis of important natural products.