Author ORCID Identifier

Defense Date


Document Type


Degree Name

Doctor of Philosophy



First Advisor

Dr. Joshua D. Sieber

Second Advisor

Dr. Julio Alvarez

Third Advisor

Dr. Frank Gupton

Fourth Advisor

Dr. Brian Fuglestad


Most natural products and other biologically active small molecules contain multiple stereogenic heteroatoms throughout their carbon scaffold. As a result, methods to install these multi-heteroatom functionalities efficiently are highly desirable. Reductive coupling reactions have been studied extensively, and reductive allylation has been a key method for generating chiral secondary and tertiary allylic alcohols. This work focuses on utilizing naturally abundant and inexpensive Cu for the asymmetric reductive coupling of alleneamides with carbonyl electrophiles to access highly functionalized multi-heteroatom scaffolds that are difficult to produce via traditional methods. Described herein are methods for these asymmetric reductive coupling reactions. Chapter 1 describes the development of CuH-catalyzed methods for the regio- and diastereoselective reductive coupling of N-based allenes and carbonyl electrophiles. The method reported was the first disclosed to access the novel linear product in the reaction with ketones, as well as directly access both the traditional branched product and the novel linear product from the same system by simply tuning the ligand. Initial projects utilized stereocontrol by a chiral auxiliary, whereas subsequent projects focused on the development of chiral-ligand controlled methods utilizing an achiral alleneamide. Chapter 2 describes the branched- and enantioselective borylative Cu-catalyzed reductive coupling of an achiral alleneamide with aldehyde electrophiles utilizing B2(pin)2 as the reductant. The intermediate of these reactions contains a boronate handle that allows for further derivatization and access to a wide array of dissonant 1,2-aminoalcohol motif-containing products based solely on the workup. This work is high-yielding with high diastereo- and enantiocontrol. The Suzuki-Miyaura cross-coupling reaction is a highly utilized method for generating biaryl molecules in both industrial and academic settings. Traditional boronic acid homocoupling side product generation in these systems is due to O2 intrusion during the reaction. However, during attempts to couple two electron-deficient fragments under anaerobic conditions, the boronic acid homo-coupling and aryl halide dehalogenation side products were both observed in similarly high yields. Chapter 3 describes the discovery and development of a novel anaerobic mechanism for the generation of aryl boronic acid homo-coupling product in the Suzuki-Miyaura cross coupling reaction of electron-deficient systems. The discovery, mechanistic investigation, and scope of the optimized reaction are discussed.


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