Development and Mechanistic Investigation of Potassium Tert-Butoxide Catalyzed C–H Silylation

Abstract

The synthetic organic community has a long history of concurrent development of new methods, total syntheses, and mechanistic investigations. For example, new methods may allow the synthesis of previously inaccessible synthetic targets or a challenging transformation in a total synthesis may lead to the development of new reaction methods. Understanding the mechanism of a reaction may lead to the development of new methods or application in total synthesis. Historically, the Stoltz group has found great success focusing on the synergistic development of reaction methods, total synthesis, and mechanistic investigation. This thesis focuses on the mechanistic investigation of a novel method developed by our group and a number of new methods inspired by this better understanding of the reaction mechanism. Initially, an overview of transition-metal-free, catalytic C–H silylation reactions is presented. Next, a detailed mechanistic investigation into the KOt-Bu-catalyzed C–H silylation reaction of aromatic heterocycles is presented. This investigation covers a series of experimental, computational, and analytic techniques to probe possible radical or ionic reaction mechanisms. The development of a number of new methods is presented including the catalytic trimethylsilylation of aromatic heterocycles and catalytic silylation of terminal alkynes. Finally, the current progress of our efforts toward the total synthesis of the natural product illisimonin A are presented.