Novel Catalytic Processes Utilizing C–H and H–X Activation

This research project is devoted to investigating novel catalytic processes, utilizing CH and HX activation. The proposed investigations mainly serve to explore new chemical reactions. These reactions can make new molecules accessible, or can facilitate the production of already known molecules, and therefore improve industrial processes in an economic and ecological respect. Thus, fundamental research is essential for application in chemical and pharmaceutical industry. The catalytic nature of the reactions means that only very little reagent (for this project palladium catalyst) is needed to perform the reaction. This is very good on one hand due to the high price of palladium catalysts and on the other hand because not much of precious and possibly harmful material must be disposed. The basis for the proposed innovations come from Professor Mark Lautens, who will be the host for this project. The goal of this project is to find reliable and robust conditions to perform efficient halogen transfers between molecules. The type of conversions explored during this research project was never presented so far, therefore it could mean a big achievement to the scientific community and industry in a broader sense. The proposed reactions are developed stepwise leading to more and more complicated target structures. On a more advanced stage, the instead of hazardous acids, the use of safe and practical salts (ammonium halides) will be presented. This avoids many drawbacks associated with traditional hydrogen halides, including toxicity and corrosiveness. The methodological research will be ultimately concluded with a concise synthesis of sinomacutine D. The isolation of this natural product was reported in 2014 from Sinomenium acutum, which is endemic to southern China and Japan. This plant is used for treatment of rheumatoid arthritis, arthralgia, dermatophytosis, and paralysis in traditional folk medicine. Natural product isolation very often only offers milligram quantities of the desired material. The synthesis of this intriguing natural product will be the first practical application of the elaborated methods. This should also yield the natural product in abundance for further biological investigations. One of the synthetic routes to sinomacutine D also includes a novel variation of a Catellani reaction; a reaction which includes a CH activation. Usually CH bonds are very unreactive and such activations enable reactions on atoms that are not accessible under normal reaction conditions. Another goal is to apply the acquired knowledge in Austrian medicinal chemistry projects and further development of elaborated reactions in a collaboration with researchers from Austrian research institutions. These arrangements allow the Austrian scientific community to benefit from the learnings of this research project abroad.

This research project was devoted to investigating novel catalytic reactions, exploiting C-H and H-X activation. The project focused on research of novel palladium-catalyzed processes in a so-called domino reaction, where one chemical transformation leads into the next. Catalysis emphasizes that a reaction is facilitated by use of a catalyst which is not consumed during the course of the reaction. This is advantageous as the needed palladium catalysts that are used are usually very expensive and also less chemical waste is generated. These reactions can make new molecules accessible, or can facilitate the production of already known molecules, and therefore improve industrial processes in an economic and ecological respect. Thus, fundamental research is essential for application in chemical and pharmaceutical industry. The catalytic nature of the reactions means that only very little reagent (for this project palladium catalyst) is needed to perform the reaction. The innovations in this project are building on previous findings and we will see if these innovations themselves will achieve a big reception in academic research or in industry. The novel chemical reactions have the potential to resemble advancement for science and industry. Further, in the course of the project also other towards other research subjects were investigated. In a medicinal chemistry project, inhibitors for an enzyme which is often mutated in patients with Alzheimer's disease but is also favoring metastases in cancer cells. The aim is to provide a probe for the enzyme free of charge for all researchers. Also, contributions towards a total synthesis were part of the project, with the aim to synthesize a complex natural product. The synthesis will also comprise an early application of the elaborated methods. A chemical engineering project was also supported. The aim was to modify a known and licensed drug in a way that it still keeps it's potency but that it forms a colloid at given pH-values. In this way the drug should be transformed into a transport form which facilitates better transportation. Then, once the drug reaches the intended target it should be transformed again into the non-colloidal form, triggered by change in pH-value. The gained learnings were implemented in methodological projects in Austria during the return phase. This way also Austrian researchers had access to the knowledge gained abroad.