Development of a multistep, electrochemical flow platform for automated catalyst screening

Schotten, Christiane; Manson, Jamie A.; Chamberlain, Thomas W.; Bourne, Richard A.; Nguyen, Bao; Kapur, Nikil; Willans, Charlotte E.

doi:10.1039/d2cy00587e

Cited by 9 publications

(4 citation statements)

References 62 publications

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“…A range of additional transformations are emerging as opportunities toward scalable processes (e.g., electrochemical trifluoromethylation of heterocycles, hydrogenations − ) that may be of high interest to pharma. The electrosynthesis of catalysts , and ligands , for catalysis and the deployment of asymmetric electrocatalytic methods are also of interest, but examples of these on large scale are still scarce. The development of electrosynthetic processes in green solvents is also of interest.…”

Section: Discussionmentioning

confidence: 99%

Overview of Recent Scale-Ups in Organic Electrosynthesis (2000–2023)

Lehnherr,

Chen

2024

Org. Process Res. Dev.

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This review summarizes examples of organic electrosynthesis from the peer-reviewed literature from 2000 to 2023 that have been conducted on scales of 20 g or above. A significant portion of these examples were conducted on a ≤100 g scale, while detailed reports of kilogram-scale electrosynthesis remain scarce in the pharmaceutical industry. In addition to the chemical transformation, this review also highlights the type of reactor used and a projected productivity metric as ways to compare the different reports. The selected examples of organic electrosynthesis scale-ups described herein also illustrate the remaining challenges currently preventing the routine use of large-scale electrosynthesis in the pharmaceutical industry.

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Section: Discussionmentioning

confidence: 99%

Overview of Recent Scale-Ups in Organic Electrosynthesis (2000–2023)

Lehnherr,

Chen

2024

Org. Process Res. Dev.

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“…For example, Willans et al. developed a multistep electrochemical flow platform for the automated screening of metal‐NHC catalysts [25] . In contrast to chemical reagents, electrons are not converted into side products, and can therefore be classified as clean reagents.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Willans et al developed a multistep electrochemical flow platform for the automated screening of metal-NHC catalysts. [25] In contrast to chemical reagents, electrons are not converted into side products, and can therefore be classified as clean reagents. Hence, the electrochemical synthesis of metal-NHC complexes enables direct addition into subsequent steps without purification, which is ideal for telescoped continuous flow processes.…”

Section: Continuous Flow Platformsmentioning

confidence: 99%

Recent Developments in Reactor Automation for Multistep Chemical Synthesis

Clayton

2023

Chemistry Methods

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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.

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“…For example, Willans and coworkers designed a multistep flow platform used to electrochemically generate copper catalysts. 15 Their reactor was built up of circular stacked copper electrodes separated by polytetrafluoroethylene (PTFE) spacers. With a reactor volume of 0.9 mL, each flow electrolysis needed 23 min to reach completion (1.8 h to reach steady state).…”

mentioning

confidence: 99%