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

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.