This dissertation describes the development of reaction methodologies that utilize unconventional building blocks. One major effort involves the development of a strategy to improve the practicality of the nickel-catalyzed Suzuki–Miyaura cross-coupling of amide electrophiles and a strategy for a base-mediated reduction of ketones to secondary alcohols. Furthermore, a one-pot reductive arylation of amides wherein two different nucleophiles are added to the amide carbonyl carbon is reported. This reaction, which proceeds by way of a sequential nickel-catalyzed Suzuki–Miyaura coupling and base-catalyzed reduction cascade process, directly converts amide starting materials to chiral secondary alkyl–aryl alcohol products. Finally, investigations into strained heterocyclic allenes are described. These studies detail the cyclic allene approach to the core of the manzamine alkaloid keramaphidin B, where the key step hinges on a cycloaddition of an azacyclic allene intermediate. Furthermore, the parameters controlling the regioselectivity of the Diels–Alder cycloaddition of heterocyclic allenes with a-pyrones is reported. Each of the methodologies presented is expected to expand the synthetic toolbox by leveraging unique reactivity.