Key points are not available for this paper at this time.
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.
Norman et al. (Fri,) studied this question.