UC Irvine

This dissertation details the development of a synthetic route to the pleuromutilin diterpenes and the discovery of catalyst-controlled radical‒polar crossover reactions of allylic alcohols. Chapter one outlines the isolation and structure determination, biosynthesis, and antimicrobial activity of the pleuromutilins. Additionally, analysis of the unique chemistries and existing synthetic approaches to the mutilin diterpenoids is provided. Chapter two delineates our analysis of the pleuromutilin structure and execution of a new synthetic approach. Beginning with our early attempts to assemble the polycyclic architecture, the evolution of our strategy through three distinct phases is described. The culmination of these studies is a 16-step stereocontrolled synthesis of pleuromutilin, the shortest to date. Chapter three is comprised of relevant background to Markovnikov-selective radical hydrofunctionalization reactions and our laboratory’s studies on the radical‒polar crossover reactions of allylic alcohols. Our observation of previously unprecedented catalyst control over the radical‒polar crossover reactions of dialkyl(vinyl)carbinols is outlined.