As discussed previously, there are two main positions of diversity within MPAA ligands: the α-carbon and the acetamide protecting group. Hence, to separate their influence on reaction outcome, both positions were parameterized separately for each ligand rather than using a single descriptor for the entire molecule. As the ligand's steric profile was expected to influence reaction yield greatly, two steric descriptors were introduced, Sterimol and percentage buried volume (%VBur) . Sterimol descriptors 29 quantify steric demands along different principal axes, making them well-suited to describing the steric effects of unsymmetrical substituents. The percentage buried volume is a descriptor that is traditionally used for catalyst-ligand complexes and describes the percentage of the volume of a sphere that is occupied by a given substituent. We used the a-carbon/[N-residue] as centre of our sphere and the calculation was performed considering only the variable residue extending from this position. In addition to this, a number of electronic descriptors were calculated for the ligand molecules as the fine-tuned electronics can impact Lewis basicity of the two binding atoms (N and O) and the aptitude to engage in the key mechanistic step (concerted metalation deprotonation, CMD). To capture the electron density distribution, we calculated the HOMO/LUMO energies and conducted a NBO analysis (Natural Bond Orbital) and a CHELPG analysis (CHarges from ELectrostatic Potentials using a Grid-based method).