Different Oxidative Addition Mechanisms for 12- and 14-Electron Palladium(0) Explain Ligand-Controlled Divergent Site Selectivity

In cross-coupling reactions, dihaloheteroarenes are usually
most
reactive at C–halide bonds adjacent to a heteroatom. This selectivity
has been previously rationalized. However, no mechanistic explanation
exists for anomalous reports in which specific ligands effect inverted
selectivity with dihalopyridines and -pyridazines. Here we provide
evidence that these ligands uniquely promote oxidative addition at
12e– Pd(0). Computations indicate that 12e– and 14e– Pd(0) can favor different mechanisms
for oxidative addition due to differences in their HOMO symmetries.
These mechanisms are shown to lead to different site preferences,
where 12e– Pd(0) can favor oxidative addition at
an atypical site distal to nitrogen.