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

Abstract

Carbon-carbon cross-coupling reactions are among the most important processes in organic chemistry and Suzuki-Miyaura reactions are the most widely used protocols. For a decade, green chemistry and particularly catalysis and continuous flow, have shown immense potential in achieving the goals of "greener synthesis". To date, it seems difficult to conceive the chemistry of the 21st century without the industrialization of continuous flow process in the area of pharmaceuticals, drugs, agrochemicals, polymers, etc. A large variety of palladium Suzuki-Miyaura cross-coupling reactions have been developed using a continuous flow sequence for preparing the desired biaryl derivatives. Our objective is to focus this review on the continuous flow Suzuki-Miyaura cross-coupling using homogeneous and heterogeneous catalysts.

The kinetics and mechanism of polymer‐based NHC‐Pd‐pyridine catalyzed heterogeneous Suzuki reaction in aqueous media

“…Reductive elimination is the final step (Step 4) of the catalytic cycle, which generates the coupling product Ar−Ar′ by elimination from a palladium complex on the catalyst. After the product is released from the palladium complex, the catalytic cycle has been completed, and the reformed palladium complex can perform another cycle …”

High Throughput Experimentation and Continuous Flow Validation of Suzuki–Miyaura Cross‐Coupling Reactions

“…Microfluidic reaction evaluation of the HTE hits are an essential step for validating organic transformations under continuous flow conditions. This has been shown to be especially true for catalytic reactions that can be achieved under faster and greener conditions . Moreover, fast microfluidic synthesis of small organic molecules, coupled with continuous reaction monitoring using electrospray ionization mass spectrometry (ESI‐MS), shows even greater promise for rapid optimization of continuous production methodology .…”

“…The S‐M reaction has already been reported under some limited ranges of flow conditions, nonetheless, we explored its utility toward the synthesis of important synthons in a microfluidic reactor using EtOH as solvent to broadly explore the utility of this transformation …”

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

“…Examples of Suzuki-Miyaura reactions are reported in [74], which consist in coupling organoboron compounds with aryl, alkenyl and alkynyl halides. Typically, a homogeneous approach is used, but heterogeneously catalysed reactions were recently proposed [75].…”

“…Nevertheless, stronger efforts should be put in the definition of experimental correlations for a wider applications window. Len et al [74]. Reproduced from [74] under the terms of the Creative Commons Attribution License.…”