Use of “Homeopathic” Ligand-Free Palladium as Catalyst for Aryl-Aryl Coupling Reactions

We have previously shown that the use of ligand-free palladium employing Pd(OAc)2 as catalyst precursor in the Heck reaction of aryl bromides is possible if low catalyst loadings, typically between 0.01 – 0.1 mol % are used. We have now tested this phenomenon, which we have dubbed “homeopathic” palladium, in biaryl formation using the Suzuki, the Negishi and the Kumada cross-coupling reactions. The Suzuki reaction of aryl bromides, both activated and deactivated, is possible using 0.02–0.05 mol % of Pd(OAc)2. In this reaction turnover frequencies up to 30,000 have been reached with activated substrates. Even aryl chlorides could be reacted if strongly electron-withdrawing substituents were present. The Negishi coupling with a variety of arylzinc halides was possible on aryl bromides containing electron-withdrawing substituents. The Kumada reaction only gave low yields of products under “homeopathic' conditions.