Development of Facile and Simple Processes for the Heterogeneous Pd-Catalyzed Ligand-Free Continuous-Flow Suzuki–Miyaura Coupling

The Suzuki–Miyaura coupling reaction is one of the most widely utilized C–C bond forming methods to create (hetero)biaryl scaffolds. The continuous-flow reaction using heterogeneous catalyst-packed cartridges is a practical and efficient synthetic method to replace batch-type reactions. A continuous-flow ligand-free Suzuki–Miyaura coupling reaction of (hetero)aryl iodides, bromides, and chlorides with (hetero)aryl boronic acids was developed using cartridges packed with spherical resin (tertiary amine-based chelate resin: WA30)-supported palladium catalysts (7% Pd/WA30). The void space in the cartridge caused by the spherical catalyst structures enables the smooth flow of a homogeneously dissolved reaction solution that consists of a mixture of organic and aqueous solvents and is delivered by the use of a single syringe pump. Clogging or serious backpressure was not observed.