Small molecules continue to be a stronghold for innovation in the chemical industry. Molecular design is at the heart of two businesses with an enormous impact on human health and well-being: drug discovery and agrochemistry. These industries rely on the ability to systematically explore novel chemical matter in order to find novel properties. The current business model can be summarized as a two-step process: (i) finding a basic molecular framework with interesting properties, and (ii) decorating that ‘lead scaffold’ with different functionalities and substituents to improve its properties. This tried-and-tested approach has created huge amounts of economic value, and has quite literally saved millions of lives. The modern paradigm of molecular design, often paraphrased as ‘exploring chemical space’, has seen diminishing returns in recent decades. To some extent, innovation is struggling with the limited diversity of new compounds that are being screened. Especially the bias of such compounds towards sp2-rich ‘flat’ heterocyclic scaffolds is thought to be a poor match for the intricate 3D-structures of their protein targets. This project aims to develop synthetic tools that allow the transformation of flat heterocyclic scaffolds, prevalent in modern screening libraries, into well-defined 3D-scaffolds, by the targeted decoration of unsaturated bonds with a small-size ring fusion. For this, novel cycloaddition reagents will be developed based on thionium ions.