Mastering Palladium Catalyzed Cross-Coupling Reactions: The Critical Role of In Situ Pre-catalyst Reduction Design.

Abstract

Palladium catalyzed cross coupling reactions are among the most used methods for carbon-carbon bond formation in the agrochemical and pharmaceutical segments. The key step common to all methodologies based on Pd(0) catalysis is the generation in situ of the active catalyst. The paper describes how to control pre-catalysts reduction in order to generate the target complex species avoiding phosphine oxidation or, as in the case of the Heck-Cassar-Sonogashira and the Suzuki-Miyaura reactions, reactants consumption via dimerization. For PPh3, DPPF, DPPP, Xantphos, SPhos, RuPhos, XPhos and sSPhos we identified protocols able to maximize the reduction via alcohol preserving ligands and reagents. The correct combination of counterion, ligand, and base allowed to perfectly control the Pd(II) reduction to Pd(0) in the presence of primary alcohols.