Klumpp, Douglas A.
Ph.D. (Doctor of Philosophy)
Department of Chemistry and Biochemistry
Synthetic organic chemistry is a vital part of the modern world – making up 15-20% of the U.S. economy. New synthetic reactions can lower manufacturing costs and create more environmentally friendly processes. Substitution, addition, and superelectrophilic chemistry are potent tools to afford potentially essential compounds. The work outlined in this dissertation recounts the expansion of synthetic methodologies employing substrates with a wide range of electrophilicities toward synthesizing heterocyclic molecules. These concepts are summarized in chapter 1. Chapter 2: N-Heterocyclic alcohols are excellent substrates for superacid-promoted Friedel-Crafts reactions. The N-heterocyclic alcohol ionizes to produce reactive, dicationic intermediates, providing good to excellent arylation product yields. Chapter 3: N-heterocyclic nonclassical carbocations form regioselective Friedel-Crafts products. Dicationic 2-norbornyl carbonium ions were generated in superacidic conditions and provided good to excellent yields of arylation products. Chapter 4: Cyclopropylmethyl carbonium ions form regioselective and thermodynamically controlled alkenes and tetralins. The arylation products are formed in nearly quantitative yields. Di and tricationic species are proposed intermediates for the Friedel-Crafts conversions. Chapter 5: A variety of 9,9’-spirobifluorenes and related azaspirocycles and diazaspirocycles have been prepared in high yields by intramolecular Friedel-Crafts reaction using the Brønsted superacid, triflic acid (CF3SO3H). Compared to weaker Brønsted acids, the superacid consistently provides better yields along with reduced reaction times and eliminates the need for heating. The superacid is particularly effective when dicationic electrophilic intermediates are generated in the conversions, for example, with the diazaspirocycle syntheses. Chapter 6: Spirooxindoles, constituted through a spiro-fusion of a heterocyclic or carbocyclic ring at the 3-position of an oxindole, are privileged, three-dimensional structures often found in pharmaceutically important molecules. A variety of spirooxindoles have been prepared by Nazarov cyclization using the Brønsted superacid, triflic acid (CF3SO3H). Chapter 7: A series of conjugate addition reactions with vinyl-substituted N-heterocycles. Double conjugate addition reactions have been accomplished using active methylene compounds to provide dipyridyl and related heterocyclic products. These conversions have utilized 1,3-dicarbonyl compounds, cyano esters, cyano sulfone, and malonyl nitrile as nucleophiles. The Michael accepting groups include vinyl-substituted pyridines, quinoline, and pyrazine. Chapter 8: 3D printed plastics were used as substrates to generate a solid acid catalyst for flow chemistry. These catalysts were utilized in synthesizing drug precursors, commodity chemicals, and OLED molecules using a variety of acid-catalyzed conversions. The 3D-printed catalyst was demonstrated to be reusable, providing the potential for large-scale green chemistry.
Hood, Jacob C., "Synthetic Methodologies Using Nucleophile-Electrophile Chemistry" (2023). Graduate Research Theses & Dissertations. 7150.
Northern Illinois University
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