Pd-Leaching and Pd-Removal in Pd-Catalyzed Suzuki Couplings

Jeng-Shiou Chen1, Oleksiy Vassylyev1, Anthony Panarello2, and Johannes Khinast1. (1) Chemical & Biochemical Engineering, Rutgers, the State University of New Jersey, 98 Brett Road, Piscataway, NJ 08854, (2) Merck & Co., Inc., 770 Sumneytown Pike, P.O. Box 4, West Point, PA 19486

Suzuki couplings have proven efficient for the preparation of biologically active compounds1, such as tyrosine kinase inhibitors2 and the phosphodiesterase IV inhibitor3. Suzuki couplings are also important for the development of supported catalysts, e.g., for the immobilization of ansa-ethylene-bis(indenyl)-metal complexes onto heterogeneous supports4. Among all catalysts for Suzuki couplings, palladium on carbon (Pd/C) is favored for industrial applications, due to its high catalytic activity and ease of use. It is a heterogeneous catalyst, and thus, is easily removed from the reaction mixture. However, some studies5 indicated that palladium leaches from the carbon support and that the leached colloidal Pd catalyzes the reaction. After the reaction is completed, it is believed to partially re-adsorb back on the carbon support. Although Pd-leaching has been documented, the mechanism of Pd-leaching during Suzuki couplings has not been investigated in detail. Therefore, the objective of this work is to provide a detailed understanding of Pd-leaching in Pd/C-catalyzed Suzuki couplings. Furthermore, we intend to provide a strategy to remove Pd from the reaction mixture after the reaction has been completed.

Pd-leaching in Pd/C catalyzed Suzuki couplings is investigated by the model coupling reaction of biphenylacetic acid. Effects of reaction solvents, bases, borates and halides on Pd-leaching are discussed. Filtration tests and PVPy adsorption indicate that the main reactivity of Pd/C is due to leached Pd. Thus, Pd-leaching is necessary for the reactions. Oxidative addition of aryl-bromides in Suzuki couplings and oxidative addition of aryl-borates in self-couplings were shown to be the main causes for Pd-leaching, which is independent of the reaction solvents and the temperature. Furthermore, PVPy was proven to be a good reagent to completely remove Pd-residual from the reaction mixture; excess PVPy (4 eq. to Pd) is sufficient for complete removal in 2 hours.

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