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

Abstract

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.

Continuous flow (micro-)reactors for heterogeneously catalyzed reactions: Main design and modelling issues

“…Pd/C), but leaching remains the major point. A library of reactions and products has been recently proposed [76], as exemplified e.g. in Fig.…”

Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling in Continuous Flow

“…In their hands, the SEM analysis of SS-Pd showed the presence of Pd(0) nano-microparticulates on the solid support which implies its reusability and minimum leaching of Pd from the solid surface. Martin-Matute developed a novel strategy using Pd nanoparticles supported in a functionalized mesoporous Metal-Organic Frameworks (MOFs) [102]. To the best of our knowledge, it was the first report on the use of metallic nanoparticles supported on MOFs in flow chemistry for catalytic applications.…”

“…The authors always used the same cartridge for the preparation of the mini-library of biaryl derivatives. It is noticeable that after the reaction, the recovery catalyst was found to be partially crystalline with a remaining Pf content of 6.81 wt % (initially 7.29 wt %) [102]. Martin-Matute developed a novel strategy using Pd nanoparticles supported in a functionalized mesoporous Metal-Organic Frameworks (MOFs) [102].…”

“…It is noticeable that after the reaction, the recovery catalyst was found to be partially crystalline with a remaining Pf content of 6.81 wt % (initially 7.29 wt %) [102]. Martin-Matute developed a novel strategy using Pd nanoparticles supported in a functionalized mesoporous Metal-Organic Frameworks (MOFs) [102]. To the best of our knowledge, it was the first report on the use of metallic nanoparticles supported on MOFs in flow chemistry for catalytic applications.…”

“…A mixture of aryl halide, boronic acid/ester and K 2 CO 3 in water and ethanol was passed through a column of homemade 8 wt % Pd@MIL-101-NH 2 at room temperature for a residence time of 35-40 min (Scheme 17). Martin-Matute developed a novel strategy using Pd nanoparticles supported in a functionalized mesoporous Metal-Organic Frameworks (MOFs) [102]. To the best of our knowledge, it was the first report on the use of metallic nanoparticles supported on MOFs in flow chemistry for catalytic applications.…”