Catalysis is a key process enabling the formation of important value added products from simpler starting materials and is ubiquitous in chemical processes. Catalysis is estimated to contribute > 35 % of global GDP and recent estimates indicate that 90% of industrial chemicals are synthesized in processes that require at least one catalytic step. However, many catalysts are based on rare and expensive elements, collectively called the platinum group metals (PGMs), that have significant supply chain risks thus are classed as critically endangered raw materials by the EU. Furthermore, these elements also have significant toxicity concerns, which imposes considerable purification costs particularly in the production of pharmaceuticals. Therefore the replacement of catalysts containing PGMs with alternatives that are based only on highly abundant, inexpensive, low-toxicity elements is a crucial endeavour.
One vital catalytic process, called cross coupling, is essential across many industries as it forms carbon-carbon bonds. This Nobel prize winning chemistry is an essential tool for constructing the carbon backbone in organic-materials, pharmaceuticals and agrochemicals. The Suzuki-Miyaura (S-M) cross coupling reaction is the most prevalent cross-coupling method as it is reliable, modular and utilises low toxicity, easy to handle starting materials based on boron, termed organoboranes. S-M couplings are ubiquitous in both academia and industry, for example they are one of the top five most utilised reactions in pharmaceutical research laboratories. Despite its undeniable power there are drawbacks and limitations associated with the S-M reaction. For example, S-M couplings are currently dependent on toxic catalysts based on a rare PGM Pd, and to a lesser extent Ni (which is also highly toxic). Furthermore, while S-M couplings are very powerful for making flat (two dimensional) molecules it does not work effectively to form more three dimensional structures, which are essential as nature is three dimensional! This has led to an over-representation of flat molecules that are less “drug-like” in pharmaceutical research programs and thus there needs to be new modular methods to make C-C bonds in three dimensional structures. Therefore the important challenges addressed by this proposal are:
Overarching Objective 1: Generating S-M cross coupling process for forming C-C bonds in 3D molecules that uses low toxicity earth abundant catalysts based on zinc and boron. This objective was ultimately expanded to include the development of zinc catalysed C-H borylation processes and catalytic C-Zn bond formation.
Overarching Objective 2: Synthesising new and useful organoboranes using only simple precursors and without using PGM catalysts.
