We are grateful to the Novartis-MIT Center for Continuous Manufacturing for financial support. We thank several colleagues at MIT (Dr. Yuan Zhang, Dr. Ping Zhang, and Dr. Jie Wu) and at Novartis (Dr. Berthold Schenkel, Dr. Gerhard Penn, and Dr. Benjamin Martin) for insightful discussions.
Continuous-Flow Synthesis of Functionalized Phenols by Aerobic Oxidation of Grignard Reagents†
Article first published online: 19 FEB 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 53, Issue 13, pages 3353–3357, March 24, 2014
How to Cite
He, Z. and Jamison, T. F. (2014), Continuous-Flow Synthesis of Functionalized Phenols by Aerobic Oxidation of Grignard Reagents. Angew. Chem. Int. Ed., 53: 3353–3357. doi: 10.1002/anie.201310572
- Issue published online: 19 MAR 2014
- Article first published online: 19 FEB 2014
- Manuscript Revised: 12 JAN 2014
- Manuscript Received: 5 DEC 2013
- Novartis-MIT Center
- flow chemistry;
- Grignard reagent;
Phenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas-liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation-sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne-mediated in-line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three-step, one-flow process, capable of preparing 2-functionalized phenols in a modular fashion, is established.