Automation in multistep synthesis involves the use of robotics, advanced software, and machine learning algorithms to streamline the complex process of creating molecules. This review highlights recent advances in automated batch and continuous flow platforms, and presents how these technologies can be applied in the development and optimisation of multistep processes.
Reactor automation is revolutionising the way new chemical processes are discovered and developed. Assigning repetitive aspects of chemical synthesis to machines, such as experimental execution and data collection, provides more time for researchers to focus on critical interpretation and creative problem solving. The ability to autonomously prepare late-stage intermediates and complex products, rather than just simple starting materials, will play a central role in applications such as the efficient exploration of chemical space and responsive manufacturing. However, translating automated technologies from specific single-step tasks to more general multistep syntheses remains a significant challenge, owing to high structural diversity and chemical/physical interdependencies between the steps. Robotic batch and continuous flow platforms are gradually becoming more universal, providing access to a wider range of chemistries required to achieve autonomous multistep synthesis. Advances in process analytical technologies have enhanced our ability to monitor interconnected reactions in real-time, thus accelerating data collection and giving greater process control for ensuring a high standard of safety and product quality. Integration of these tools with control software creates a feedback loop, which can be harnessed for adaptive and flexible multistep screening or holistic self-optimisation. This review presents recent developments in the application of automated reactor technologies for multistep chemical synthesis, including batch and continuous flow platforms. Specifically, this review highlights how the integration of control software with advanced process analytical technologies and machine learning algorithms are accelerating the synthesis of complex molecules.Zum Volltext