Ligand Descriptor Analysis in Nickel‐Catalysed Hydrocyanation: A Combined Experimental and Theoretical Study

The problem of choosing the ‘right chelating ligand’ for a homogeneously catalysed reaction is outlined. A model is introduced that combines mechanistic information and ligand descriptors. This model is used together with automated synthesis tools to study the structure‐activity relationship in a diverse set of forty‐two ligands, and extract information on active regions in the catalyst space. The concept is demonstrated on nickel‐catalysed hydrocyanation, using bidentate phosphine and phosphite ligands. The charge at the ligating atoms, the rigidity of the molecules, the steric crowding around the Ni atom, and the bite angle are found to be the most important descriptors. A comparison is made with literature hydrocyanation data and approaches for designing new homogeneous catalysts are discussed.