Continuous Flow Suzuki-Miyaura Couplings Under Aqueous Micellar Conditions in a CSTR Cascade Catalyzed by Fe/ppm Pd Nanoparticles

Chemistry in water, enabled by tailor-made surfactants that form nanomicelles of a particular size and shape, has been developed to accommodate flow conditions using Fe/ppm Pd nanoparticles as catalyst for Suzuki-Miyaura reactions. Cross-couplings of this type that are heterogeneous in terms of both the substrate and catalyst are particularly troublesome under flow conditions, and pose a major challenge in continuous manufacturing of pharmaceuticals and fine chemicals. To address this major issue, a new continuous stirred-tank reactor (CSTR) cascade has been engineered that can handle slurries/solids at any point during a chemical transformation in flow. Solid starting materials are now simply suspended in water and pumped into the CSTR as a heterogeneous slurry, minimizing the upstream need for organic solvents, thereby leading to a far more environmentally friendly process. The ability of CSTR cascade to handle solids continuously was demonstrated over hours, without clogging, by examining several couplings which involve both initial solid catalyst and substrates, while generating solids products, some of which are key intermediates in pharmaceuticals currently in use