Molecular complexity via aza-Heck initiated C-H functionalization cascades

Our group develops new catalysis platforms that allow the rapid generation of pharmaceutically valuable heterocyclic scaffolds. We have reported a range of aza-Heck cyclizations initiated by oxidative addition of N-O bonds to Pd(0)-catalysts. These processes generate challenging N-heterocycles and seem well suited to medicinal chemistry. In this project we will expand the aza-Heck approach to a series of cascade reactions where C(sp3)-H functionalisation occurs after aza-palladation of an alkene. The scope of this strategy will be explored for the accessing a variety of fused N-heterobicycles, including systems containing cyclopropanes. We will also showcase the chemistry in the synthesis of a structurally complex and biologically important natural product target. The new chemistry will provide rapid access to molecular complexity within an atom economical (i.e. minimal waste) reaction design. Potential end users include chemists in the pharmaceutical industry, where the chemistry could be used for the generation of compound libraries.