Standardization and control of Grignard reactions in a universal chemical synthesis machine using online NMR

Bornemann-Pfeiffer, M., Wolf, J., Meyer, K., Kern, S., Angelone, D., Leonov, A., Cronin, L. and Emmerling, F. L. (2021) Standardization and control of Grignard reactions in a universal chemical synthesis machine using online NMR. Angewandte Chemie (International Edition), 60(43), pp. 23202-23206. (doi: 10.1002/anie.202106323) (PMID:34278673)

Abstract

A big problem with the chemistry literature is that it is not standardized with respect to precise operational parameters, and real time corrections are hard to make without expert knowledge. This lack of context means difficult reproducibility because many steps are ambiguous, and hence depend on tacit knowledge. Here we present the integration of online NMR into an automated chemical synthesis machine (CSM aka. ‘Chemputer’ which is capable of small-molecule synthesis using a universal programming language) to allow automated analysis and adjustment of reactions on the fly. The system was validated and benchmarked by using Grignard reactions which were chosen due to their importance in synthesis. The system was monitored in real time using online-NMR, and spectra were measured continuously during the reactions. This shows that the synthesis being done in the Chemputer can be dynamically controlled in response to feedback optimizing the reaction conditions according to the user requirements.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leonov, Mr Artem and Angelone, Dr Davide and Cronin, Professor Lee
• Authors: Bornemann-Pfeiffer, M., Wolf, J., Meyer, K., Kern, S., Angelone, D., Leonov, A., Cronin, L., and Emmerling, F. L.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Angewandte Chemie (International Edition)
• Publisher: Wiley
• ISSN: 1433-7851
• ISSN (Online): 1521-3773
• Published Online: 18 July 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Angewandte Chemie (International Edition) 60(43): 23202-23206
• Publisher Policy: Reproduced under a Creative Commons License