Development of Carbon‒Carbon, Carbon‒Nitrogen, and Carbon‒Hydrogen Bond Functionalization Methodologies and Efforts Toward the Total Synthesis of Dragmacidin E

Abstract

Chapter 1: this chapter introduces the area of carbon‒carbon sigma bond activation, as well as the contributions made to the field by the Douglas group. Efforts to develop a diastereoselective intramolecular alkene cyanoamidation methodology involving C‒CN bond activation are described. The development of an intramolecular alkene aminocyanation methodology utilizing N‒CN bond activation is also described. Chapter 2: this chapter provides a brief summary of the development of metal-organic cooperative catalysis approaches to bond activation and functionalization methodologies, including prior work reported by the Douglas group on the intramolecular hydroacylation of alkenes. Efforts to develop chiral organic co-catalysts for these intramolecular alkene hydroacylation reactions are also described. Chapter 3: this chapter introduces the dragmacidin family of natural products. A particular emphasis is placed on previously reported syntheses of dragmacidins D, E, and F, and how these synthetic efforts have contributed to the structural assignment of this family of natural products. Chapter 4: this chapter depicts our efforts toward the total synthesis of dragmacidin E. A retrosynthetic analysis focused on utilizing the intramolecular alkene hydroacylation methodology developed by the Douglas group is described, as well as efforts to synthesize a suitable substrate for this key synthetic step.