Selectivity for Exhaustive Cross-Coupling of Dihaloarenes is Affected by the Interplay Between Halide Byproduct, Solvent, and Ligand

In dihaloarene cross-couplings, the step(s) that take place after reductive elimination and before the start of the next cycle influence selectivity for mono- versus difunctionalization. When palladium is supported by a bulky ligand "L", a competition exists between a second oxidative addition (leading to difunctionalization) and bimolecular displacement of Pd0 from the monofunctionalized product by a second smaller ligand. Because oxidative addition of Ar-Br is faster than Ar-Cl, more difunctionalization might be expected with dibromoarenes compared to dichloroarenes. However, the opposite has been reported in some Suzuki-Miyaura cross-couplings. Here, we report that the selectivity outcome is closely tied to solvents: dibromoarenes tend to give less diarylation than dichloroarenes in oxygen-containing solvents of at least moderate polarity (e.g., THF), whereas high selectivity for diarylation can be achieved in most aromatic and chlorinated solvents. The results suggest that, in polar oxygen-containing solvents, the bromide anion byproduct displaces LPd0 from the mono-cross-coupled product. The rate of this process is competitive with the rate of intramolecular oxidative addition en route to the diarylated product. In contrast, the analogous displacement of Pd0 by chloride (the byproduct when using dichloroarenes) appears to be a much slower process, if it occurs at all.