In Chapter One a review of the paxilline indole diterpene (PID) class of secondary metabolites is provided. The review introduces the paxilline indole diterpenes and describes defining structural and biosynthetic features. Thorough analysis of the prior synthetic art offers perspective that will contextualize the synthetic efforts described by our own lab in subsequent Chapters.

In Chapter Two a structure-goal and transform-based strategy to the paxilline indole diterpenes family of secondary metabolites is described. The pursuit of a tricarbocyclic subtarget led to the development of a new regioselective alkenylation of enoxysilanes and a radical-polar crossover polycyclization cascade. Our initial efforts in this area guided the application of a tether-controlled radical conjugate addition/aldol sequence to access the common pentacyclic core of the family. Realization of our strategy resulted in an 11-step synthesis of emindole SB, which is the simplest congener of the family.

In Chapter Three efforts focused on the extension of our strategy to the paxilline indole diterpenes are described. The insight provided by previous work from our lab guided the pursuit of a radical-polar crossover polycyclization cascade that enabled the preparation of a precursor to the tetracyclic terpenoid core of 11-ketopaspaline. A diastereoselective late-stage reduction of a ketal moiety delivered an undesired epimeric terpenoid core and thwarted a potential 14-step total synthesis of 11-ketopaspaline.

In Chapter Four a brief review of cobalt-catalyzed hydrofunctionalization of alkenes utilizing a radical-polar crossover reaction manifold initiated by a chemoselective hydrogen atom transfer is described. This body of research served as inspiration for the unexpected development of a chemoselective Ritter reaction. The formation of tert-alkyl acetamides from simple alkenes is achieved under mild conditions and in the presence of acid-sensitive functional groups. Efforts toward the hydrofunctionalization of monosubstituted alkenes via discreet organocobalt(III) and cationic organocobalt(IV) complexes is also described. Experiments aimed at elucidating the reaction mechanism indicated that radical intermediates are short-lived and relevant secondary organocobalt(III) complexes are plausible intermediates.