Catalytic Advancements: Optimizing Pd-Based Cross-Coupling Reactions Through Flow Chemistry

Abstract

Flow chemistry is a method of conducting a reaction in continuous flow through channels by pumping the reactants into the system. This advanced method offers rapid and efficient mixing, precise control of reaction conditions, high-throughput screening, and rapid optimization of the reaction as compared to batch conditions. In the current times, various pharmaceutical intermediates are being produced efficiently using flow chemistry. One of the most important reactions emerging is the carbon− carbon cross coupling reaction using transition metal catalysis especially palladium. Cross-coupling reactions are vital in the creation of advanced materials with tailored properties desired for pharmaceuticals, agrochemicals, and fine chemicals. Over the years, numerous Pd-catalyzed cross-coupling reactions, such as Suzuki-Miyaura coupling, Mizoroki-Heck coupling, Sonogashira coupling, Stille coupling, Negishi coupling, etc., have been explored and widely applied. Continuous-flow methods for heterogeneous catalysis have enhanced the reaction by integrating the separation process into a single step using packed bed reactors and eliminating the need for additional steps for catalyst recovery. The focus of this review is to address various catalysts developed for Pd-catalyzed cross-coupling reactions in a flow reaction, followed by optimization such as flow rate, residence time, temperature, Pd loading, solvent, base, and concentration of starting material. This review presents a comprehensive study of these catalysts used for C−C coupling using flow chemistry.