UC Berkeley

The scope of my doctoral studies was intended to address the specific synthetic challenge of the construction of heterocycles. As a result, the synthesis of nitrogen-containing heterocycles has been a key research focus during my graduate career and with this in mind, new methods for their construction were investigated.

In Chapter 1 of this dissertation, an aminoarylation reaction methodology was developed. This system utilized gold catalysis to accomplish an intramolecular aminocyclization followed by a aryl cross-coupling event to accomplish an overall aminoarylation. The strong oxidant Selectfluor was chosen as the terminal oxidant in the reaction due to its previous use in metal- catalyzed reactions. Experimentation and literature precedent led to the use of a bimetallic gold complex to facilitate the Au(I)-Au(III) oxidation which is typically a synthetic challenge. An unusual reaction mechanism was proposed for this reaction as a result of experimental probing in conjunction with a series of DFT calculations. This oxidative gold-catalyzed aminoarylation was found to provide access to a variety of heterocycles in a racemic fashion.

The second chapter continues with the theme of aminocyclization reactions but focuses on developing an asymmetric methodology. Previous work in our group had shown that dicationic Selectfluor is insoluble and generally unreactive in non-polar organic solvents. This reagent could be rendered useful after undergoing a phase-transfer event when used with lipophilic chiral phosphoric acids and accomplishing an enantioselective fluorination. However only cyclizations involving oxygen nucleophiles were disclosed. With this in mind, studies were undertaken to extend this phase-transfer technology towards aminocyclization reactions. It was found that an enantioselective 1,4-fluoroamination reaction could be accomplished with different diene substrate scaffolds.

Chapter 3 concentrates on another extension of the phase-transfer methodology utilizing a aryldiazonium salts. Literature precedent had shown that the terminal nitrogen of these reagents could serve as electrophiles for carbon-based nucleophiles, and their monocationic nature would allow for them to be sparingly soluble in organic solvents, thus revealing them as ideal candidates for phase-transfer reactivity. The reaction of these electrophilic nitrogen sources with tryptamine-based substrates allowed for the enantioselective construction of C3-functionalized pyrroloindolines which are an exotic framework found in natural products. The diazenated pyrroloindoline products could be further elaborated using photochemistry to provide C3-arylated compounds, exhibiting the versatility of this methodology for the construction of C-C or C-N bonds at the C3 position on the pyrroloindoline scaffold.