Polarity Reversal Catalysis in Organic Electrosynthesis

Organic chemistry has unfortunately not the best reputation. People talk excessively about toxic chemistry and unhealthy chemicals. Albeit, it is often forgotten that our own body is an incredibly complex chemical facility and that the technological developments in organic chemistry lead to the improvement of billions of lives. Most modern medicinal drugs for instance would be unthinkable without our knowledge about organic chemistry. However, the environmental damages caused by the chemical industry are commonly known. This urges scientist to search for alternative methods in which potentially harmful chemicals can be avoided. Oxidation- and reduction processes produce an extraordinary amount of chemical waste, because only a tiny fraction of the oxidants/reductants mass is used during the reaction. Only the movement of small elementary particles (electrons) is really of decisive importance. This is why electrosynthesis is such a vibrant and promising field of research: instead of using potentially dangerous chemicals, the electrons coming from a common socket are used. Moreover, this approach is enabling reactions, which are not possible under conventional conditions. The research conducted under the supervision of Prof. Phil Baran at the Scripps institute in La Jolla, California focuses on these interesting concepts. More specifically, electrosynthesis is used in order to synthesize natural products and pharmaceutical drugs. As an Erwin-Schrödinger fellow I hope to optimize important chemical processes in the long term in order to make chemical transformations more benign to the environment.

During the COVID-19 pandemic the world witnessed an unprecedented pace in the development of new vaccines and pharmaceuticals to fight this new disease. The fast development of new drugs and agrochemicals is an interdisciplinary effort in which synthetic organic chemistry plays a key role because it is considered the toolbox of medicinal and agrochemists to build the active ingredients of their field. The here presented project focused on the development of a totally new concept for the synthesis of certain motifs of organic molecules. This concept does not only help chemists to access new ways of putting their active ingredients together because these newly developed reactions are much more selective and mild, tolerating a wide range of substrates but also enables them to do this in a much safer and environmentally friendlier way. Instead of using toxic, expensive and reactive chemicals to access certain reactive intermediates which are a necessity for certain very important chemical reactions, electricity was used: a metal catalyst is usually activated with a reductant which contains a hydrogen atom to form the active species (a transition metal hydride) to be engaged in a transformation of a chemical substrate. This means that the smallest possible molecular entity (a hydrogen atom) has to be usually transferred from a much bigger and more complex dangerous chemical, leading to large amounts of chemical waste to finally modify the substrate. In this work the catalyst is simply activated by electrical current. The activated catalyst can then simply take the hydrogen atom from a mild acid in form of a proton to yield the same reactive transition metal hydride. The mild acid is less dangerous, cheaper, can be easily regenerated and does not lead to large amounts of chemical waste. Leading experts in 5 different institutions helped to elucidate the fundamentals of the new concept with an intriguing mechanistic diversity of those reactions. Although this concept was studied extensively during this project, it might open up an infinite number of new transformations since it can be easily tuned and modified by varying the used catalyst and also the substrates used for these reactions.