Automation and Microfluidics for the Efficient, Fast, and Focused Reaction Development of Asymmetric Hydrogenation Catalysis
Robbert van Putten, Natalie S. Eyke, Lorenz M. Baumgartner, Victor Schultz, Georgy A. Filonenko, Klavs F. Jensen, Evgeny A. Pidko
Abstract
Abstract Automation and microfluidic tools potentially enable efficient, fast, and focused reaction development of complex chemistries, while minimizing resource‐ and material consumption. The introduction of automation‐assisted workflows will contribute to the more sustainable development and scale‐up of new and improved catalytic technologies. Herein, the application of automation and microfluidics to the development of a complex asymmetric hydrogenation reaction is described. Screening and optimization experiments were performed using an automated microfluidic platform, which enabled a drastic reduction in the material consumption compared to conventional laboratory practices. A suitable catalytic system was identified from a library of Ru II ‐diamino precatalysts. In situ precatalyst activation was studied with 1 H/ 31 P nuclear magnetic resonance (NMR), and the reaction was scaled up to multigram quantities in a batch autoclave. These reactions were monitored using an automated liquid‐phase sampling system. Ultimately, in less than a week of total experimental time, multigram quantities of the target enantiopure alcohol product were provided by this automation‐assisted approach.