DOI
https://doi.org/10.25772/CEJ9-V720
Author ORCID Identifier
https://orcid.org/0000-0002-7135-0505
Defense Date
2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Chemistry
First Advisor
Dr. Joshua D. Sieber
Abstract
Many drugs and natural products contain multiple stereogenic carbons bearing heteroatoms throughout their carbon framework. Therefore, methods that can efficiently install multiple heteroatoms on a molecule are valuable. Reductive coupling reactions have been extensively studied, and the allylation of carbonyls via the reductive coupling approach has been a key method for generating chiral tertiary and secondary allylic alcohols. This work utilizes inexpensive Cu for the asymmetric reductive coupling of allenamides with carbonyls to simultaneously install two heteroatoms (oxygen and nitrogen) on the product. These molecules have a polarity profile that make them difficult to make using traditional methods. Herein, we report a method for the asymmetric reductive coupling reactions. Chapter 1 describes the development of a regiodivergent and diastereoselective CuH-catalyzed reductive coupling of N-based allenes and carbonyls, where stereoselectivity is controlled by a chiral auxiliary and regioselectivity is modulated by catalyst tuning through choice of ligand. This protocol provides access to novel linear and branched products. The linear products underwent standard chemical transformations to furnish (S)- boivinianin-A, a natural product with a γ-lactone motif. Chapter 2 details the development of the first asymmetric enantioselective aminoallylation of ketones, which features the first reported case of a reversible aminoallylation event in reductive coupling processes. This protocol provides an atom-economical approach for the synthesis of 1,2-aminoalcohols. The reaction paradigm was expanded to incorporate aldehydes as electrophiles to asymmetrically produce secondary alcohols.
The Buchwald Hartwig Amination is a powerful reaction for the synthesis of aryl amines. They are extensively used in industrial processes. Currently, homogeneous catalysts are more active and selective than heterogeneous catalysts and are therefore favored in industrial processes. Unfortunately, the use of homogeneous organic palladium complexes as catalysts incurs costs in downstream purification processes when removing palladium impurities. Heterogeneous catalysis faces no such issues because it is easily removed via filtration. These heterogeneous catalysts also have the added benefit of reusability, which makes the development of such a system valuable. Chapter 3 describes our efforts to develop a heterogeneously catalyzed Buchwald-Hartwig Amination employing nanoparticles synthesized via the Strong Electrostatic Absorption method as a catalyst. The development of this reaction, scope, and recycling studies are discussed herein.
Rights
© Raphael Kwaku Klake
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-12-2023