Abstract: This dissertation describes our development of an efficient and scalable synthesis of the caged tetracyclic antiviral diterpenoids wickerols A and B. Our first-generation synthesis of these natural products was achieved by leveraging the diverse reactivity of alkenes in productive C–C bond forming events, including: (1) a conjugate addition to construct a key quaternary stereogenic center; (2) a reductive samarium(II) iodide-mediated ketyl radical cyclization of a keto-enoate progressing through divergent reaction mechanisms depending on additive selection; (3) an aliphatic Claisen-rearrangement-based sequence to install a methyl-bearing stereogenic center with simultaneous formal homologation of an aldehyde that was recalcitrant to direct methylation; and (4) an interrupted chlorinative Prins reaction/controlled dehydrochlorination process for bridging ring construction in the face of strain-driven carbocation rearrangements. We embarked on a convergent second-generation synthesis of the wickerols implementing a concise, tandem radical bicyclization-based approach for rapid construction of the carbon scaffold. The discovery of a deleterious 1,5-hydrogen atom transfer pathway precluded this proposed radical bicyclization, and investigation of alternative stepwise approaches to ring system construction led to the observation of a fused 5/6/7 tricyclic core formed through a samarium(II)-iodide-mediated ketyl radical cyclization proceeding with undesired 7-endo regiochemistry. A redesigned second-generation synthetic strategy informed by these results hinging upon a polarity-matched ketyl radical cyclization was devised. This revised strategy was reduced to practice with the successful construction of the fused 6/6/5 ring system embedded in the carbon skeleton. Elaboration to intermediates suitable for closure of the final bridging ring of the wickerols and our initial investigation of this ring closure are described.