Selective halogenation of pyridines and diazines via unconventional intermediates
Date
2022
Authors
Levy, Jeffrey N., author
McNally, Andrew, advisor
Bandar, Jeffrey, committee member
Neilson, Jamie, committee member
Hansen, Jeffrey, committee member
Journal Title
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Volume Title
Abstract
Pyridines and diazines are prevalent in pharmaceuticals, agrochemicals, ligands, and other organic materials, and it's vital that synthetic chemists can selectively functionalize these heterocycles. We have shown that heterocyclic phosphonium salts and Zincke imine intermediates can be used to regioselectively functionalize pyridine rings. This dissertation describes the development of these strategies with an emphasis on new approaches to selectively halogenate pyridines, which we view as a long-standing challenge in organic chemistry. Chapter One introduces the importance of pyridines and diazines, as well as established methods and limitations in halogenating these azines. Chapter Two provides an overview of the synthesis and reactivity of heterocyclic phosphonium salts, and then describes a new strategy to access 4-halogenated pyridines via these reagents. Chapter Three examines further developments of heterocyclic phosphonium salts, including as how they can be used to selectively add amines and fluoroalkyl substituents to pyridines. Chapter Four provides an overview of pyridine ring-opening reactions and then shows how this approach can be applied to selectively halogenate the 3-position of pyridines. Chapter Five describes how modifications to the ring-opening strategy can be used to change halogenation site-selectivity. This chapter also shows that the ring-opened intermediates can be used to form isotopically labeled pyridines and aniline derivatives.
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Embargo Expires: 08/22/2024
Subject
diazines
iodination
pyridines
halogenation
chlorination
phosphonium