Continuous-Flow Synthesis of Functionalized Phenols via Aerobic Oxidation of Grignard Reagents

Angewandte Chemie 53(13), 3353-3357, DOI: 10.1002/anie.201310572

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.