Parameterization of phosphine ligands reveals mechanistic pathways and predicts reaction outcomes

The mechanistic foundation behind the identity of a phosphine ligand that best promotes a desired reaction outcome is often non-intuitive, and thus has been addressed in numerous experimental and theoretical studies. In this work, multivariate correlations of reaction outcomes using 38 different phosphine ligands were combined with classic potentiometric analyses to study a Suzuki reaction, for which the site selectivity of oxidative addition is highly dependent on the nature of the phosphine. These studies shed light on the generality of hypotheses regarding the structural influence of different classes of phosphine ligands on the reaction mechanism(s), and deliver a methodology that should prove useful in future studies of phosphine ligands. The choice of ligand used in a reaction can drastically influence the overall outcome. Using a combination of classic physical organic chemistry and modern mathematical modelling, phosphine ligand effects are probed. The methods described provide the groundwork for future mechanistic studies of this ubiquitous ligand class.