Flow Chemistry for Flowing Cross-Couplings: A Concise Overview

Abstract

Cross-coupling reactions have revolutionized synthetic chemistry by significantly expanding the scope of carbon–carbon (C–C) and carbon–heteroatom bond formation, making them invaluable tools in the design and synthesis of pharmaceuticals, natural products, and advanced materials. Despite recent advancements in making these reactions more sustainable, some challenges remain, such as the requirement for high temperatures and extended reaction times. In recent decades, flow chemistry has emerged as a powerful solution, with microreactor technology offering numerous advantages for cross-coupling reactions. These include improved reaction efficiency, better heat and mass transfer, and the potential for more environmentally friendly conditions. This review aims to provide a concise and up-to-date guide on recent advancements in flow chemistry as applied to Pd-catalyzed cross-coupling reactions, including Suzuki, Heck, Sonogashira, Negishi, Stille, and Buchwald couplings. By presenting unified schemes for these reactions, the aim of this review is to provide quick and helpful comparisons to readers in order to select optimal reaction conditions based on their starting materials, streamlining the decision-making process in synthetic chemistry.