Designing Pd and Ni Catalysts for Cross-Coupling Reactions by Minimizing Off-Cycle Species

This Perspective presents an overview on recent experimental and computational studies on the off-cycle reactions of palladium- and nickel-catalyzed cross-couplings. Several reactions entering or leaving the catalytic cycle have been characterized, including the activation of Pd(II) precatalysts by H-shift and the deactivation of Ni(II) precatalysts by comproportionation. A fundamental difference between the off-cycle chemistries of palladium and nickel is the larger diversity of species yielded by the latter, with a rich combination of different oxidation states, nuclearity, and ligand coordination modes. The molecular-level understanding of off-cycle reactions has been exploited in catalyst design, including the stereoelectronic fine-tuning of the ligands aimed at maximizing the activation of the precatalyst meanwhile preventing its deactivation. Despite several challenges, which concern both experiments (e.g., isolation and characterization of transient species) and computations (e.g., comprehensive mapping of the potential energy surface), this approach has already been applied with success in the optimization of popular catalytic platforms (e.g., NHC–Pd–allyl precatalysts) and shows promise for the development of highly active and robust catalysts based on nickel.