Heteroatom Annulations: The Catalytic Synthesis of Heterocycles

The importance of heterocyclic compounds cannot be overstated; around one half of all known organic compounds contain a heterocyclic ring. These compounds, be they natural products or designed molecules, are responsible for an amazing variety of biological processes and they feature in the majority of pharmaceuticals. They are also used as agrochemicals, colourants and as new materials. The synthesis of heterocyclic compounds has a long and extensive history in which many classic syntheses have been developed, however significant challenges still remain, with certain compound classes remaining difficult to prepare. Modern discovery chemistry also places new demands on synthetic routes, requiring rapid access to related structures through simple late-stage modifications. In this proposal we present new methodology that allows access to a variety of heterocyclic systems using a single strategy. In the process we open new classes of heterocycle precursors and also allow access to structures that have traditionally presented considerable challenges.The proposed methodolgy combines two simple established transformations to generate a powerful new method for heterocycle synthesis. The method is based on the use of tandem palladium catalysis, and crucially allows a whole variety of different heterocycles to be accessed from a single class of precursor. We will also demonstrate how this new method can be used to prepared extremely challenging heterocyclic target systems.