Thompson, Severin Kelly2019-08-202019-08-202019-07https://hdl.handle.net/11299/206360University of Minnesota Ph.D. dissertation.July 2019. Major: Chemistry. Advisor: Thomas Hoye. 1 computer file (PDF); xvii, 302 pages.Cycloaromatization reactions yield cyclic products that are aromatic but unstable, leaving these products prone to further reactions and functionalization. Their relevance in the antibiotic mechanism of enediyne natural products as well as their ability to access diversely functionalized arenes have made cycloaromatization reactions a point of significant focus in chemical research. One particularly interesting and synthetically valuable cycloaromatization reaction is the hexadehdyro-Diels–Alder (HDDA) reaction, in which a 1,3-diyne moiety engages a covalently attached alkyne (diynophile) in a formal [4 + 2] cycloaddition under thermal conditions. The product of this reaction, 1,2-didehydrobenzene—also known as benzyne—is capable of reacting with myriad “trapping” molecules to yield an array of functionalized benzenoid products. This HDDA cascade, as well as other related cycloaromatization reactions, are the focus of this thesis. Reactions of HDDA-generated benzyne with various carbonyl moieties were studied. Among these benzyne-trapping reactions are “divergent” reactions, in which HDDA-generated benzyne is shown to react differently from benzyne generated by the more standard Kobayashi protocol. Additionally, novel benzyne reactions that are not reported in the literature are discussed (Chapter 2). Closely related to the HDDA reaction is the pentadehydro-Diels–Alder (PDDA) reaction, in which a 1,3-allenyne (as opposed to a 1,3-diyne) undergoes a [4 + 2] cycloaddition with a pendant alkyne to yield a precedented but understudied ,3-dehydrotoluene intermediate. Synthetic studies of this reaction revealed its ability to access functionalized benzene and pyridine products, while computational studies lent insight into its mechanism and energetics (Chapter 3). Finally, the incorporation of nitriles into the HDDA reaction was investigated. The replacement of an alkyne with a nitrile on either the diynophile or 1,3-diyne of an HDDA substrate gives aza-HDDA substrates that cyclize to 3,4-pyridyne (Chapter 4) and 2,3-pyridyne (Chapter 5) intermediates. The generation of these intermediates and their subsequent trapping reactions to produce diversely functionalized pyridine products are discussed.enThesis or Dissertation