Project: Dearomative cycloadditions: finding novel reactivity in well-known chemical space

2020-01-01 – 2023-12-31

Abstract

Aromatic rings are structural strongholds in biologically relevant molecules They are essential substructures in proteins and nucleic acids, and take a prominent place in metabolites and small molecule drugs Conventionally, (hetero)arenes are considered as robust, rigid and structurally well-defined (bio)molecular substructures, important for molecular recognition and metabolic stability

In chemistry, aromatics are known as synthetically versatile compound classes, which are easy to make, and easy to modify Aromatic derivatisations exploit the reactivity of the conjugated electronic systems, and often rely on the strong tendency to retain or reform the aromatic system, limiting the number of viable reaction pathways with highly activated reagents Reactions that reliably transform ‘lat’(hetero)arenes into three-dimensionally intricate ring systems, are thermodynamically and mechanistically challenging, and few examples are known, although they are very useful and conceptually attractive synthetic methods

This project will build on expertise in the use of triazolinediones and allyl cations as highly activated reagents that have been found, in isolated cases, to reliably dearomatise furans, indoles, or simple arenes, giving access to fused saturated ring systems Taking a bottom-up approach, this project will expand this type of reactivity to a wider range of substrates, by developing novel reagents as potent ‘hetero)arenophiles'