Continuous-Flow Technology for Chemical Rearrangements: A Powerful Tool to Generate Pharmaceutically Relevant Compounds

The efficacy, safety, and scale-up of several chemical rearrangements remain unsolved problems due to the associated handling of hazardous, toxic, and pollutant chemicals and high-risk intermediates. For many years batch processes have been considered the only possibility to drive these reactions, but continuous-flow technology has emerged, for both academic laboratories and pharmaceutical companies, as a powerful tool for easy, controlled, and safer chemistry protocols, helping to minimize the formation of side products and increase reaction yields. This Technology Note summarizes recently reported chemical rearrangements using continuous-flow approaches, with a focus on Curtius, Hofmann, and Schmidt reactions. Flow protocols, general advantages and safety aspects, and reaction scope for the generation of both privileged scaffolds and active pharmaceutical ingredients will be showcased.

Automated summary

The handling of hazardous, toxic, and pollutant chemicals and high-risk intermediates remains a challenge for the efficacy, safety, and scale-up of chemical rearrangements. However, continuous-flow technology has emerged as a powerful tool for driving these reactions, offering easy, controlled, and safer chemistry protocols with minimal side products and increased reaction yields. This Technology Note provides an overview of recent chemical rearrangements using continuous-flow approaches, focusing on Curtius, Hofmann, and Schmidt reactions, and showcases their advantages, safety aspects, and applications in generating privileged scaffolds and active pharmaceutical ingredients.