Metal Electronics Mediate Steric and Coordination Number Effects on Palladium(II) C-X Reductive Elimination

Reductive elimination is the key bond-forming elementary step in many transition metal-catalyzed reactions relevant to the synthesis of pharmaceuticals, materials and fine chemicals. Metal electronics, ancillary ligand sterics and metal complex coordination number have been identified as the primary factors which affect the rate of reductive elimination, but their relative importance has not been quantified. By studying a new class of palladacycles using kinetics, electrochemistry, DFT calculations and tools from causal inference, we reexamine the canonical model and find that a direct effect of coordination number on rate is unlikely. To address this contradiction, we propose an updated understanding based on mechanistic considerations, which accounts for our findings, the canonical understanding, and other observations in literature. Path coefficients calculated using mediation analysis allow the quantification of the effects of electronics, sterics and coordination number on the rate. Overall, we find that electronics and changes in coordination number exert the greatest influence on the rate, with the latter primarily acting through altering metal electronics. Finally, using this new-found knowledge, we were able to use the structures of complexes reported in the literature to calculate appropriate DFT descriptors and build a model capable of predicting the rate of reductive elimination for C-N, C-S and C-O bond formation with reasonable accuracy.