(1) The first total syntheses of glycoborinine, clausenawalline A, and clausenawalline E were achieved. The key step employed a vanadium-catalyzed oxidative coupling of two hydroxycarbazole monomers. High-throughput experimentation was used to identify conditions favoring selective heterocoupling of these monomers that possess similar redox potentials. A combination of a vanadium catalyst and 4-acetamido-TEMPO gives rise to greatly enhanced cross selectivity relative to the vanadium catalyst alone. Conditions to selectively form homodimer clausenawalline A or heterodimer clausenawalline E as the major product were found.(2) (a) Hydrogen bonding is a key factor in the design of ligands for biological binding, including drug targets. Our group previously developed a method for experimentally assessing the hydrogen-bond-donating ability using UV–vis titrations with a colorimetric sensor. Using this method, 79 new titrations were performed on weak, biologically relevant hydrogen-bond donors. The hydrogen-bond donating abilities of drug compounds and the substructures of drug compounds were also measured. (b) Trifluoromethyl ketones (TFMKs) readily form stable hydrates and hemiketals in solution, allowing them to interact with biomolecules as hydrogen-bond donors. This interaction is governed by both the hydration equilibrium and the hydrogen-bonding strength for a given compound. The hydrogen-bond-donating abilities for aryl, heterocyclic, and alkyl TFMKs were evaluated. Values were adjusted based on the percent hydrate present in solution to provide insight into the hydrogen-bond-donating ability of the hydrate species. (3) The cyclization of medium-sized biaryl rings presents a longstanding challenge in synthetic chemistry due to entropic penalties and unfavorable ring strain. The biosynthesis of cyclic diarylheptanoids, a class of bioactive natural products, involves cyclization via an intramolecular oxidative phenol coupling, which inspired our efforts to reproduce this transformation synthetically. Numerous oxidative conditions were screened but were low-yielding due to competing intermolecular coupling pathways. To promote intramolecular coupling, pre-organization strategies using molecular containers, including cyclodextrins and metal-organic frameworks (MOFs), were explored. While cyclodextrins were capable of guest binding, they failed to improve selectivity. MOFs exhibited low reactivity, likely due to insufficient guest encapsulation. These studies highlight the difficulty of achieving selective macrocyclization via oxidative coupling and suggest that more effective templating methods, such as enzymes, are required.