Reworking Organic Synthesis for the Modern Age: Synthetic Strategies Based on Continuous-Flow Addition and Condensation Reactions with Heterogeneous Catalysts.

While organic synthesis carried out in most laboratories uses batch methods, there is growing interest in modernizing fine chemical synthesis through continuous-flow processes. As a synthetic method, flow processes have several advantages over batch systems in terms of environmental compatibility, efficiency, and safety, and recent advances have allowed for the synthesis of several complex molecules, including active pharmaceutical ingredients (APIs). Nevertheless, due to several reasons related to the difficulties arising from byproduct formation during the flow process, such as lower yields, poor selectivities, clogging of columns due to poor solubility, catalyst poisoning, etc., successful examples of continuous-flow synthesis of complex organic molecules are still limited. In order to solve this bottleneck, the development of selective and atom-economical continuous-flow organic transformations are needed. This perspective highlights examples of atom-economical addition and condensation reactions with heterogeneous catalysts under continuous-flow conditions and their applications for the synthesis of complex organic molecules such as natural products and APIs. In order to realize new continuous-flow methodologies, based on addition and condensation reactions, in place of substitution reactions, the development of novel reactions and heterogeneous catalysts is required.