Effective BI-DIME Ligand for Suzuki-Miyaura Cross-Coupling Reactions in Water with 500ppm Palladium Loading and Triton X

An efficient, sustainable, and broadly applicable procedure has been developed for Suzuki-Miyaura cross-coupling reactions in environmentally benign solvent (water) by employing as little as 500ppm Pd(OAc)(2) with a monophosphorus BI-DIME ligand in the presence of inexpensive and commercially available nonionic surfactant TritonX-100. This method was applied to a broad range of functionalized reaction partners, thereby affording excellent yields of the coupling products, including active pharmaceutical ingredients (APIs). An interesting kinetic study by using reaction calorimetry is also presented, which describes the effect of reaction parameters that enabled the low catalyst loading.