(Georgia Institute of Technology, 2022-09-07)
Chen, Doris
Heterocycles and carbocycles often exhibit remarkable structural features as well as propitious bioactivities that attract immense attention from the synthetic community. These motifs also constitute the core framework of many natural products and synthetic pharmaceuticals. For these reasons, a great need exists for the exploration and development of robust synthetic protocols that efficiently access these frameworks. In this thesis, heterocycles and carbocycles will be accessed in unprecedented ways by leveraging the reactivity of 1,3-dipoles, specifically in the form of N-alkoxyazomethine ylides and oxyallyl cations.
Projects in all three realms of organic synthesis research will be discussed: (1) exploratory chemistry/methodology discovery, (2) methodology development, (3) target-oriented synthesis. First, in collaboration with Pfizer Inc., an exploratory project was initiated to study the generation and reactivity of novel N-alkoxyazomethine ylides in cycloaddition reactions to render nitrogen-containing heterocycles. In the second project, the first intramolecular, interrupted, formal homo-Nazarov cyclization methodology was developed. The method’s intramolecular oxyallyl cation trapping ability allowed facile access to complex (hetero)aryl-fused polycycles and led to a concise total synthesis of an antibacterial natural product, (±)-1-oxoferruginol. Third, in a target-oriented synthesis project, the progress made toward a key fragment in the total synthesis of an anticancer natural product, propolisbenzofuran B, using a homo-Nazarov cyclization approach, will be recounted.