New and Improved gamma-Lactam Forming Reactions: Methodology and Total Synthesis

The development of new and stereoselective chemical transformations and their application to complex targets is the main objective of a synthetic organic chemist. By discovering new reactions and/or expanding upon current methodology, the possibilities for synthesis of structurally interesting targets can grow. This dissertation describes the challenges of organic chemistry in both total synthesis and method development. Chapter one describes the first diasteroselective synthesis of heliotropamide, whose gamma-lactam core was assembled using a four-component reaction (4CR) developed in the Shaw lab. Chapter two describes the synthesis of non-natural alkaloids using a reaction between an imine and cyclic anhydride to form gamma-lactams (imine-anhydride reaction). Chapter three describes the use of thiols as chiral auxiliaries in both our 4CR and imine-anhydride reactions, while chapter four discusses the development of a new gamma-lactam forming imine-anhydride reaction using cyanosuccinic anhydride. The research described in this dissertation represents a fundamental advance in the assembly of highly substituted gamma-lactams and the subsequent chemistry of these products.