1,4–Conjugate Addition with Pyrrole and Indole Enones & Propargylic Substitution using Boronic Acids as Nucleophiles with Gallium and Silver Catalysts

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This dissertation covers two projects: 1,4–conjugate addition on pyrrole and indole enones, and propargylic substitution using boronic acid as nucleophiles and silver/gallium catalysts. b-(2-indole)-enones and b-(2-pyrrole)-enones, both historically problematic substrate types with 1,4–conjugate addition reactions, were extensively examined. Analysis of isomer- related reaction rate trends showed that proximity of a heteroatom to the enone b-carbon was favorable to reaction rate and increased resonance electron donation also increased reaction rate. These enantioselective conjugate addition reaction were ultimately enhanced by using a less electron deficient catalyst and a base additive, ammonium carbonate. After many reactions and substrates were studied, this base was shown to have an advantage effect on enhancing the conjugate addition reaction but had an adverse effect on the starting material, which lead to other side reactions with this conflicted system. For the second project, three methods have been developed for nucleophilic propargylic substitutions that have been useful in forming tertiary carbons: (IPr)GaCl3/AgSbF6 with boronic acid at 23°C, AgSbF6 with boronic acid at 40°C, and GaCl3 with boronic acid at -78°C. A combination of AgSbF6 and IPrGaCl3 along with boronic acids at lower temperatures have been shown to decrease reaction times for the formation of nucleophilic substitution through the displacement of propargylic alcohols. GaCl3 with boronic acid at -78°C proved to be the best conditions for the formation of the quaternary carbon centers. An expanded substrate scope and nucleophile scope have been developed for the formation of the tertiary carbon centers and quaternary carbon centers using these three method

conjugate addition, propargylic substitution
Portions of this document appear in: Boylan,A.;Nguyen,T.S.; Lundy, B.J.; Li, J.-Y.; Vallakati, R.; Sundstrom, S.; May, J.A. Rate Dependence on Inductive and Resonance Effects for the Organocatalyzed Enantioselective Conjugate Addition of Alkenyl and Alkynyl Boronic Acids to β-Indolyl Enones and β-Pyrrolyl Enones. Molecules 2021, 26, 1615.