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Site-selective functionalization of azines and polyazines via heterocyclic phosphonium salts




Dolewski, Ryan D., author
McNally, Andrew, advisor
Paton, Robert, committee member
Henry, Chuck, committee member
Kanatous, Shane, committee member

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Pyridine and diazines are frequently found in FDA approved drugs, biologically active compounds, agrochemicals, and materials. Given the importance of these structural motifs, direct methods that selectively functionalize pyridine and diazine scaffolds have been developed. These methods and their associated challenges are discussed in chapter one. In chapter two, a strategy to directly and selectively functionalize pyridines and diazines via heterocyclic phosphonium salts is presented. The process is broadly applicable for pyridines and diazines and the late-stage functionalization of pharmaceuticals. Four reaction manifolds are amenable to transforming heterocyclic phosphonium salts into valuable derivatives. In chapter three, inherent factors that control site-selectivity in polyazine systems are described along with mechanistically driven approaches for site-selective switching, where the phosphonium ion can be predictably installed at other positions in a polyazine system. The fourth chapter focuses on a new strategy to selectively alkylate pyridines via a traceless dearomatized phosphonium salt intermediate. Preliminary studies show this protocol is amenable to building-block pyridines, drug-like fragments and pharmaceuticals. A late-stage methylation strategy is also presented.


2020 Spring.
Includes bibliographical references.

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