Part I: The Development of the Organocatalytic Asymmetric Mannich and Sulfenylation Reactions Part II: Progress Towards the Synthesis of Lagunamide A

Abstract

This dissertation deals with the development of asymmetric carbon-carbon and carbon-heteroatom bond-forming reactions and the synthesis of Lagunamide A. Asymmetric C-C and C-X bond formations are critical transformations in synthetic chemistry. While a variety of approaches are available to effect such reactions, organocatalytic methods have attracted considerable recent attention. Common themes have emerged from these studies with regard to both the mode of asymmetric catalysis and the nature of the substrates they are applied to. We have been investigating alternatives to these themes for both carbon-carbon and carbon-heteroatom bond formation. We will describe some of our efforts to expand the parameters of asymmetric organocatalysis, which include the development a novel biomimetic proximity-assisted soft enolization approach to the asymmetric Mannich reaction, as well as the use of nitrosoalkenes for the asymmetric a-sulfenylation of ketones and aldehydes. Lagunamide A was recently isolated from Palau Hantu Besar, Singapore and has shown strong antimalarial activity and cytotoxicity against leukemia. The work presented describes the progress towards the first asymmetric total synthesis of this natural product.