Conformation Dependent Features of Bisphosphine Ligands

Phosphines are a ubiquitous class of ligand in transition-metal (TM) catalyzed reactions. Data-driven methods using feature databases have shown promise in expediting the selection of optimal ligands for various catalytic processes. However, feature development can be challenging as many phosphine-based ligands, exemplified by bisphosphines, have diverse structural features resulting from their conformationally dependent reactivity. We present here an automated conformational analysis workflow to overcome this challenge in which a conformational ensemble of surrogate palladium-bisphosphine complexes was constructed and featurized. The resulting database contains 78 features for 147 commercially available bisphosphines, including ferrocene and atropisomeric ligands. The conformational dependence of the features is discussed and then compared in multivariate linear regression (MLR) models for an enantioselective Hayashi-Heck reaction, which resulted in improved performance using conformation-dependent features.