Rhodium-Catalyzed Carbocyclization Reactions of Alkylidenecyclopropane-Tethered Dienes

Abstract

Higher-order transition metal-catalyzed carbocyclization reactions represent an important class of reactions for the construction of complex polycyclic scaffolds not attainable by conventional pericyclic reactions. The following thesis outlines our efforts in the development of a novel rhodium-catalyzed carbocyclization reaction for the construction of both 5,5- and 5,7-bicyclic scaffolds, inherent within the scaffolds of many biologically active natural products. This thesis is divided into two chapters: Chapter 1 first highlights key developments in our understanding of the reactivity of transition metals towards alkylidenecyclopropane (ACP) and their derivatives. This pioneer work sets the stage for the systematic review of significant advances in metal-catalyzed [(3+2)] and [3+2+2] carbocyclization reactions involving ACP-tethered substrates that follows. The limitations of these advances, specifically with respect to recent advances in the [(3+2+2)] and [(3+2)] carbocyclization reactions, set the stage for our development of rhodium-catalyzed variants of these processes in Chapter 2. Chapter 2 highlights our efforts in the development of highly regio- and diastereoselective rhodium-catalyzed [(3+2)] and [(3+2+2)] carbocyclization reactions of ACP-tethered dienes. First, we describe our development of robust reaction conditions for both the [(3+2)] and [(3+2+2)] processes. Secondly, we demonstrate the extension of our developed methodology towards a broad diversity of synthesized ACP-tethered dienes. Thirdly, we present our efforts towards an enantioselective [(3+2+2)] transformation using a novel rhodium chiral diene complex. Lastly, we discuss future developments in the preceding processes.