Heterogeneous catalysis for C-C coupling reactions: insights, main drawbacks and DFT modeling perspectives.

The C-C cross-coupling reactions are organometallic condensation reactions between two organic groups, borne by two different substrates, and catalyzed by transition metal-based catalysts. They were discovered in the 20th century and gained great importance later, thanks to the agrochemical and pharmaceutical industries. Nowadays, these industries exploit the reactions for substituting complex and not eco-friendly steps of common organic synthesis paths, with greener ones. Indeed, once well-understood, this group of reactions allows to work under mild conditions, even with non-toxic solvents like water. During the last years, the most utilized catalytic systems were in-solution solubilized homogeneous systems, namely phosphine-based complexes of palladium. Though, heterogeneous catalysis offers a valuable alternative, in terms of ease in recycling the catalyst, purifying the liquid phase and isolating the reaction product. For this purpose the CSIRO laboratories patented new modular 3D-printed metallic structures, improving both the fluidodynamics of continuous reactors and the mechanical properties of the solid support, commonly used for heterogeneous catalysis applications. These structures are named Catalytic Static Mixers (CSMs). Herein an analysis of the state-of-the-art regarding the heterogeneous catalysis of cross-coupling reactions, is performed. Then, the definition of the concept of "cocktail" catalysis helps understanding more deeply, the drawbacks linked to the leaching phenomenon, which decreases the efficiency of the solid-phase catalysts. Moreover, some insights on the DFT molecular modeling techniques complete the overview on the issues which may be encountered during such applications, and their causes.