How to approach flow chemistry

Abstract

Flow chemistry is a widely explored technology whose intrinsic features both facilitate and provide reproducible access to a broad range of chemical processes that are otherwise inefficient or problematic. At its core, a flow chemistry module is a stable set of conditions – traditionally thought of as an externally applied means of activation/control (e.g. heat or light) – through which reagents are passed. In an attempt to simplify the teaching and dissemination of this field, we envisioned that the key advantages of the technique, such as reproducibility and the correlation between reaction time and position within the reactor, allow for the redefinition of a flow module to a more synthetically relevant one based on the overall induced effect. We suggest a rethinking of the approach to flow modules, distributing them in two subclasses: transformers and generators, which can be described respectively as a set of conditions for either performing a specific transformation or for generating a reactive intermediate. The chemistry achieved by transformers and generators is (ideally) independent of the substrate introduced, meaning that they must be robust to small adjustments necessary for the adaptation to different starting materials and reagents while ensuring the same chemical outcome. These redefined modules can be used for single-step reactions or in multistep processes, where modules can be connected to each other in reconfigurable combinations to create chemical assembly systems (CAS) targeting compounds and libraries sharing structural cores. With this tutorial review, we provide a guide to the overall approach to flow chemistry, discussing the key parameters for the design of transformers and generators as well as the development of chemical assembly systems.