Highly Functionalized Biaryls via Suzuki-Miyaura Cross-Coupling Catalyzed by Pd@MOF under Batch and Continuous Flow Regimes

A diverse set of more than 40 highly functionalized biaryls was synthesized successfully through the Suzuki-Miyaura cross-coupling reaction catalyzed by Pd nanoparticles supported in a functionalized mesoporous MOF (8 wt% Pd@MIL-101(Cr)-NH2). This could be achieved under some of the mildest conditions reported to date and a strong control over the leaching of metallic species could be maintained, despite the presence of diverse functional groups and/or several heteroatoms. Some of the targeted molecules are important intermediates in the synthesis of pharmaceuticals and we clearly exemplify the versatility of this catalytic system, which affords better yields than currently existing commercial procedures. Most importantly, Pd@MIL-101-NH2 was packed in a micro-flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chemistry for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large-scale applications.