Development of Catalytic Conjunctive Cross-Coupling Reactions and Progress Towards the Total Synthesis of the Sarcodictyins

Abstract

This dissertation describes the development of a method for the stereoselective synthesis of organoboronates and the applications of these products to target-oriented synthesis. The first chapter discusses an investigation of the palladium-catalyzed conjunctive cross-coupling reaction by kinetic analysis. This reaction enables the asymmetric synthesis of organoboronates by utilizing the 1,2-metallate rearrangement of borates as a mechanistic step in a cross-coupling reaction. The second chapter describes the application of the conjunctive cross-coupling reaction to the asymmetric synthesis of tertiary boronic esters. In chapter three, the conjunctive cross-coupling reaction of 1,2-disubstituted alkenyl boronates is presented. Such a substrate class is susceptible to the undesired Suzuki-Miyaura cross-coupling reaction, and this challenge led to the development of a novel diol ligand for boron as an effective solution. The final chapter details the progress toward the total synthesis of the sarcodictyin natural products, which display promising anti-cancer activity. The synthetic route utilizes reactions of organoboronates for powerful C–C bond formations; the construction of a fully-cyclyzed advanced intermediate is achieved in eight steps.