(102f) Water Soluble Palladium-?-Cyclodextrin Complex and Its Catalytic Performance for a Suzuki-Miyaura Cross-Coupling in Flow

Palladium is routinely used in homogeneous catalytic carbon-carbon cross-couplings.^1,2 As an example, the Suzuki-Miyaura cross-coupling involves the reaction of an organic halide with an organoboron compound. Hydrophobic dialkyl phosphines have been demonstrated as effective ligands for the cross-coupling, yet inorganic salt by-products are problematic in continuous-flow processes.³ The reactions are versatile in the preparation of fine chemicals, materials, natural products, and pharmaceuticals.¹

The use of water soluble catalyst is attractive because it offers a way to ensure the solubility of inorganic by-products that clog reactors.^4,5 Palladium(II)-β-cyclodextrin is such a catalyst reported to be effective in Suzuki-Miyaura hetero-couplings in batch reactors.⁵ Cyclodextrins (CDs) have a cyclic structure with a hydrophilic external rim and a hydrophobic internal cavity. The use of β-CD as a ligand allows competitive yields of cross-coupling reactions in water even at low catalyst loadings (~0.001 mol%). What’s more, the catalyst maintains high catalytic activity after recycling.⁵ The ligand has the potential for application in manufacturing processes, but the reaction kinetics are not well understood.

A capillary microreactor experiment was design to study the kinetics of the Suzuki-Miyaura using Pd(II)-β-cyclodextrin catalyst. Microreactors can expedite kinetic information compared to traditional batch reactors.Rapid mixing and heat transfer by conduction enable the design of ideal reactors for screening economical ligands. In the present study, a water-ethanol solvent system was explored as a potential reaction medium. The cross-coupling using natural product ligand was examined for the first time in continuous-flow. These results will be presented and discussed.

References:

1. Suzuki, A. Cross-coupling reactions of organoboranes: An easy way to construct C-C bonds (Nobel Lecture). Angew. Chem. Int. Ed. 50, 6723–6733 (2011).
2. Negishi, E. I. Magical power of transition metals: Past, present, and future (Nobel Lecture). Angew. Chemie - Int. Ed. 50, 6738–6764 (2011).
3. Domier, R. C., Moore, J. N., Shaughnessy, K. H. & Hartman, R. L. Kinetic analysis of aqueous-phase Pd-catalyzed, Cu-free direct arylation of terminal alkynes using a hydrophilic ligand. Org. Process Res. Dev. 17, 1262–1271 (2013).
4. Hailes, H. C. Reaction solvent selection: The potential of water as a solvent for organic transformations. Org. Process Res. Dev. 11, 114–120 (2007).
5. Kaboudin, B., Salemi, H., Mostafalu, R., Kazemi, F. & Yokomatsu, T. Pd(II)-β-cyclodextrin complex: Synthesis, characterization and efficient nanocatalyst for the selective Suzuki-Miyaura coupling reaction in water. J. Organomet. Chem. 818, 195–199 (2016).