This dissertation encompasses several studies pertaining to natural product total synthesis, reaction methodology development, and organic materials. Given that natural product structures inspire the development of new agrochemicals and pharmaceuticals, their syntheses remain a worthwhile pursuit in organic chemistry. Furthermore, the successful completion of a total synthesis endeavor can confirm proposed molecular structures and biological activities, in addition to serving as a testing ground for new synthetic methods. Similarly, organic materials impact many areas of humanity, including technology, health, and energy conversion. Therefore, developing new reaction methodologies is crucial for expanding the architectures, and thereby properties, of organic materials. Specifically, photocatalysts and organic light-emitting diodes (OLEDs) often rely on photophysical properties imparted by N-containing polycyclic aromatic hydrocarbon (PAH) ligands. As such, new methods that provide access to unique N-containing heterocyclic scaffolds are highly desirable. Chapter one offers a current perspective on the field of natural product total synthesis. Although historically viewed as a highly competitive field, several recent syntheses demonstrate a growing spirit of collaboration in total synthesis. By forming alliances with chemists in other fields, industries, or laboratories, total synthesis chemists have made many breakthroughs that would arguably not have been possible if working independently. Chapter two describes our laboratory's total syntheses of several bioactive akuammiline alkaloids, including strictamine, 2(S)-cathafoline, akuammiline, -akuammigine, and 10-demethoxyvincorine. Our strategic approach to the natural products focused on the use of a modern variant of a classic reaction, the Fischer indolization, to install several rings and the common quaternary center found in each target. This strategy allowed for the first total syntheses of akuammilines bearing a methanoquinolizidine core, as well as those that bear vicinal quaternary centers. In addition, rearrangements of the methanoquinolizidine core were developed that allowed us to access pyrrolidinoindoline-containing akuammilines. Chapter three describes synthetic studies of the reactive intermediates 2,3-pyridyne and 4,5-pyrimidyne. Heterocycles bearing one or more nitrogen atom are privileged motifs in natural products and pharmaceuticals. Therefore, methodologies that decorate such heterocycles are of great interest to the synthetic and biological communities. Arynes are highly reactive, transient species that can efficiently build multiple bonds in a single transformation, and our lab is particularly interested in accessing new, heterocyclic arynes to study their reactivity. This study demonstrates the synthetic utility of 2,3-pyridyne and the undesired reactivity of a 4,5-pyrimidyne precursor. Chapter four describes synthetic studies toward the development of new methods to manipulate polypyridyl organometallic scaffolds. Ruthenium- and iridium-based polypyridyl organometallic complexes have been known for nearly a century and have broadly impacted the scientific community, including the areas of catalysis, bioimaging, and energy conversion. Despite decades of study, methods to synthesize polypyridyl ligands are limited to relatively few transformations, particularly when extending -conjugation. We detail the use of arynes to extend the conjugation of polypyridyl ligands "on-the-complex," thereby overcoming traditional limitations in ligand synthesis. We also disclose the first generation and trapping of a ligand-bound aryne on an organometallic complex. Chapter five describes the synthesis of a novel -extended carbazole ligand for the study of structure-property relationships in two-coordinate metal complexes. Recently, linear two-coordinate metal complexes of the general structure donor-metal-acceptor have been identified as promising dopants for OLEDs. Both the donor and acceptor ligand play a crucial role in tuning the photophysical properties of these complexes. However, donor ligands with extended -conjugation have not been studied in this context. Our approach leverages heterocyclic arynes to synthesize -extended donor ligands in a modular fashion, which can also apply to other PAHs. Subsequent photophysical studies of -extended two-coordinate metal complexes identify a new dopant that displays up to 80% photoluminescence efficiency.