Natural Product Synthesis and Development of Novel Reaction Methodology

Abstract: This thesis deals with the development of new reaction methodology for stereoselective synthesis, as well as total synthesis of natural products and investigations of the stereochemical outcome in the Mukaiyama aldol reaction. Chapter 2 describes efforts made towards the total synthesis of the oxindole natural products perophoramidine and the communesin. The first part of this chapter aims to develop a domino carbopalladation-carbonylation reaction using tetrasubstituted olefins for the installation of the vicinal quaternary stereocenters of the target compounds. This approach was ultimately unsuccessful using tetrasubstituted olefins. The second part of this chapter instead relies on a Diels-Alder reaction for the installation of the quaternary stereocenters, and also describes the attempts made to reach the target compound from the Diels-Alder adduct. Chapter 3 concerns the investigation of 1,2- and merged 1,2- and 1,3-asymmetric induction in Mukaiyama aldol additions to α-heteroatom and α,β-heteroatom substituted aldehydes, respectively. In particular, the unexpected 1,2-syn selectivity obtained in the addition of sterically hindered nucleophiles to α-chloro aldehydes is studied, and an explanation for the observed stereochemical trends is proposed. Chapter 4 describes the development of a novel entry to anti-α-amino-β-hydroxy esters by 1,3-dipolar cycloadditions of aldehydes and azomethine ylides, generated by thermolysis of aziridines.