Ion-Directed Base Metal Catalysis

In Nature, many substances occur in pairs that behave like an image and a mirror image, similar to the left and right hands. The reason for this is the spatial arrangement of the atoms in the molecules. Molecules that have this property are called enantiomers. Although these enantiomers do not differ in their atomic building blocks, but only in their spatial arrangement, they can have very different effects on living things. Examples of this are the caraway-smelling (+)-carvone and its mint-smelling enantiomer (-)-carvone. Although the enantiomers can differ greatly in a biological context, they are often difficult to separate chemically. In chemical production (synthesis), it is therefore ideal to only obtain the desired enantiomer, so that separation is not necessary. Over the last few decades, several methods have been developed that produce only one of the two enantiomers in a highly selective manner. Some of the inventors were even awarded the Nobel Prize for these inventions (e.g. Chemistry Nobel Prize 2005 and 2021). Traditionally, these methods often rely on creating an environment in the chemical reaction that only allows for the production of one enantiomer through a narrow space. A bit like pressing plasticine into a mold. This works very well in some chemical reactions, but less so in others. This project takes a new, complementary approach. Instead of creating a space during the reaction that only allows one arrangement of the enantiomer, during the reaction a molecular environment is created that arranges the atoms at certain points of the molecule through strong attraction in such a way that only one enantiomer is formed. So, in a figurative sense, the previously mentioned plasticine is not pressed into a given shape, but rather pulled in a certain direction. This has been previously demonstrated in the group of Prof. Dr. Robert Phipps at the University of Cambridge (GB) using precious metals (iridium and rhodium). The combination of these metals with organic molecules, so- called ligands, leads to complexes that ultimately have the property of being able to pull the plasticine. In this project, the inexpensive base metals copper and nickel are to be examined. With the help of this fundamentally different approach, the researchers hope to be successful in chemical reactions that were difficult or impossible to implement using traditional methods.

The exploration of new chemical reactions is an important task of contemporary research. Invention of new pathways allows us to develop new compounds, which are potentially useful in a medicinal or agricultural context, or synthesize existing molecules in a more efficient an eco-friendly way. In the 6 months of this fellowship, an approach relying on ion pairing was explored. Initially, the use of metal catalysts which had been modified as such that they interact through ionic forces (+ attracts -) were investigated. Then, the use of organic molecules which can be activated with light to form an ionic intermediate was explored. The particular reaction under investigation is the so-called deracemization of alcohols. Alcohols are a chemical functional group (carbon bound to OH) which is common in biologically active compounds such as small molecule pharmaceutics or sugars. Often, they are either right- or left-handed which can have an extreme effect on the biological activity. Currently an approach is being developed which allows the selective conversion of one into the other, a previously extremely challenging endeavour, circumventing the need for their selective assembly during the synthesis. The research in the Phipps group focuses on the in-depth understanding of the underlying mechanisms in this process as, so far, our knowledge of the individual chemical steps involved is limited. Therefore, the development of this methodology is now further funded by a MSCA fellowship by the European Commission.