Simple, highly active palladium catalysts for ketone and malonate arylation: Dissecting the importance of chelation and steric hindrance

A remarkably active catalyst system for alpha-arylation of ketones and malo nates was developed by proposing that sterically hindered alkylphosphines w ould accelerate the catalytic reaction rates. We initially tested the bisph osphine ligand (DBPF)-B-t (1,1'-bis-(di-tert-butylphosphino)ferrocene) for this palladium-catalyzed chemistry. This catalyst system led to fast reacti on rates for reactions of aryl bromides with ketones, including room temper ature chemistry in many cases. In some cases turnover numbers were 20 000. The catalyst also gave mild reactions with aryl chlorides with yields that were similar to the chemistry with aryl bromides. Independent synthesis of the arylpalladium enolate complexes with isobutyrophenone enolate showed th at only one phosphorus of the bisphosphine ligand (DBPF)-B-t was coordinate d in the enolate complex. Thus, we tested sterically hindered alkylphosphin e ligands for the ketone and malonate arylation process and found that P(t- Bu)(3) gave exceptionally fast rates and high turnover numbers for these re actions. These results demonstrate several principles for the catalytic che mistry that we did not anticipate: palladium complexes of monophosphine lig ands can activate aryl chlorides under mild conditions, and palladium enola tes coordinated by certain monophosphines can undergo C-C bond-forming redu ctive elimination much faster than beta-hydrogen elimination.