Periodic Reporting for period 3 - ShuttleCat (Shuttle Catalysis for Reversible Molecular Construction) Reporting period: 2020-01-01 to 2021-06-30 Summary of the context and overall objectives of the project Homogeneous catalysis is one of the pillars of modern chemical synthesis because it enables the sustainable preparation of molecules that find applications in medicinal chemistry, agrochemistry, and materials science. However, many catalytic reactions use hazardous reagents, are unpractical on laboratory-scale or limited in scope. Moreover, while a relatively broad set of catalytic reactions are available to construct chemical bonds, methods to cleave those, which could find applications in biomass and waste valorization, are rare. The overall objective of this ERC Starting grant is to develop a conceptually new approach to catalysis which relies on the development of catalytic reversible reactions. In a first approach, shuttle catalysis reactions are targeted which offer the possibility to transfer, reversibly, toxic reagents such as HCN, CO or Cl2 between two stable chemical compounds, providing a safer approach to organic synthesis. This approach also offers new opportunities to use catalysis to either functionalize petroleum feedstocks or defunctionalize biomass-derived feedstocks. In an second approach, we also develop new single-bond metathesis reactions which allow for the reversible exchange of functional groups to enable previously unthinkable chemical transformations. Taken altogether, these new methods provide a conceptually novel entry into the safe and sustainable preparation of important organic molecules. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Several new chemical reactions have been developed since the beginning of the funding period. This includes several reactions which offer ways to avoid the use of toxic gases, including carbon monoxide and hydrogen cyanide. We have also been able to develop new single-bond metathesis reactions which offer new ways of making and breaking chemically important bonds. These new reactions effectively provide a new platform for the discovery and preparation of important compounds, such as bioactive molecules and materials. These new reactions have been published in more than 20 publications already, and the PI has presented the results at more than 50 conferences and invited lectures, including several visits to pharmaceutical and chemical companies. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) We have developed several new reactions which have clearly unlocked completely novel synthetic approaches when compared to the state-of-the-art. Many of these reactions are safer and more practical because they elude the need for toxic reagents such as CO or HCN. The metathesis reactions developed, on the other hand, allowed for unprecedented disconnections which can be used, for example, to generate drug libraries, recycle waste plastics and access challenging macrocyclic molecules.In the second part of the funding period, we expect to continue developing such novel chemical transformations. We also plan to apply some of our newly developed reactions to interdisciplinary areas, such as the preparation of new materials. This is important to demonstrate that our research will not only have a transformative impact on organic chemistry, but can also impact other research areas.