Radical Amination Strategies for the Synthesis of Nitrogen Heterocycles

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Visible light photoredox catalysis has recently emerged as a powerful method for the construction of a diverse array of molecules. The strategy uses visible light energy to generate reactive radical species that can participate in a range of bond forming reactions. The mild reaction conditions and low catalyst loadings offer more sustainable alternatives to more conventional synthetic methodologies.The amine motif is prevalent in a broad range of societally important molecules ranging from pharmaceuticals and agrochemicals, to materials to support the latest technologies. Despite this, methods for the synthesis of amines are still reliant on well-established synthetic procedures that often require the use of stoichiometric metals, toxic reagents, or starting materials that aren't readily available. Recently, it has been demonstrated that nitrogen centred radicals, generated photocatalytically under mild conditions, can add to readily available olefins providing direct access to amine derivatives. This project aims to explore the use of this strategy to enable access to pharmaceutically-relevant nitrogen heterocycles in a more concise and sustainable manner.This project will be split into two work packages: 1. Development of new strategies for the generation of nitrogen-centred radicalsA library of N-centred radical precursors bearing a range of electronically and sterically different substituents will initially be synthesised. We will then explore the use of these compounds for the introduction of amine substituents into a range of organic molecules. In particular, we will explore the development of methods for the functionalisation of readily available precursors such as olefins.2. Development of new routes to nitrogen-containing heterocycles In the second phase of the project we will explore the use of the radical amination methodology in the synthesis of amine-containing fragments and heterocycles. In particular, we will develop cascade processes that enable the rapid and efficient construction of structurally complex molecules from readily accessed precursors. Applications of the chemistry in the synthesis of bioactive molecules and pharmaceutically-relevant scaffolds will be demonstrated