A General Liquid-Liquid Partitioning Equation and Its Consequences: Learning from the pH Dependent Extraction of a Pharmaceutical Intermediate.

We observed that the product of a Buchwald-Hartwig coupling reaction extracted from the organic phase easily, relative to the starting aryl bromide as the pH was lowered. This was surprising given the similarity of their p Ka's. The product's extraction curve was also significantly steeper than expected. A consideration of the relevant equilibria, including all three of the product's p Ka's, led to a general model for the liquid-liquid extraction behavior of ionizable molecules. This model predicts the observed, useful extraction behavior.

A simple synthetic entryway into palladium cross-coupling catalysis.

The simple synthesis of a family of palladates containing an imidazolium counterion is presented. These "ate" complexes can be easily converted into well-defined palladium-N-heterocyclic carbene (NHC) complexes. The synthetic protocols leading to the "ate" and to the Pd-NHC neutral complexes have been exemplified with various NHC ligands. The palladates prove efficient pre-catalysts enabling Suzuki-Miyaura and Mizoroki-Heck reactions.

Role of the base in Buchwald-Hartwig amination.

The Buchwald-Hartwig amination has been investigated theoretically and experimentally to examine the scope of possible bases under different reaction conditions. Nonpolar solvents resist the formation of new charges. Therefore, the base should be anionic to be able to deprotonate the neutral palladium-amine complex and/or expel the anionic leaving group (bromide). The calculated barrier for the organic base DBU was found to be prohibitively high. In polar solvent, dissociation of bromide becomes possible, but here the base will instead form a complex with palladium, creating an overly stable resting state. The conclusions for both solvent classes hold for both a hindered monodentate phosphine and the labile bidentate ligand BINAP. The computational studies were supported by experimental testing of a range of bases using BINAP in two different solvents, toluene and DMF.