Highly Chemoselective Ligands for Suzuki–Miyaura Cross-Coupling Reaction Based on Virtual Ligand-Assisted Screening

Ligand screening is a crucial step in the development of transition metal catalysis, as it involves identifying the optimal ligand for a particular reaction from a large pool of candidate molecules. Conventionally, this process is performed through a time-consuming and resource-intensive trial-and-error approach. One alternative strategy for streamlining this process is a transition state theory (TST)-based approach, which aims to design optimal catalysts using quantum chemical calculations. However, TST-based ligand screening can be impractical owing to the large number of ligands that need to be evaluated through quantum chemical calculations. In this study, we present a practical TST-based ligand screening method in accordance with our virtual ligand-assisted (VLA) screening strategy. Using the chemoselective Suzuki–Miyaura cross-coupling (SMC) reaction of p-chlorophenyl triflate as the target reaction, we identified the features of phosphine ligands that maximize chemoselectivity through VLA screening. Based on the obtained results, we successfully found several ligands with high chemoselectivity. Our results suggest that the VLA screening strategy could be a useful tool for ligand screening and catalyst design.