Overcoming Challenges in Electrosynthesis Using High‐Throughput Electrochemistry: Hypervalent Iodine‐Mediated Phenol Dearomatization, a Case Study

Abstract

Abstract Despite many recent efforts, the field of organic electrosyn‐thesis faces important challenges due to the intricate nature of heterogeneous redox processes, the wide parameter space to be explored and the lack of standardized methods. To overcome these limitations, we developed a cost‐effective high‐throughput electrochemical (HTE) reactor capable of running 24 individually controlled parallel reactions. This system allows the rapid testing of electrochemical parameters on a given reaction, assessing not only yield but also reproducibility. Using the hypervalent iodine‐mediated dearomatization of phloretic acid as a demonstration of HTE capabilities, we ran more than 200 electrosyntheses in different experimental conditions and demonstrate the effect of parameters such as total charge transferred, current, electrode materials, electrolyte formulation and concentration, mediator formulation and concentration and electrochemical technique of oxidation. Notably, this report demonstrates that while catalytic amounts of iodine mediator can be used successfully, the reproducibility may be affected, which calls for a cautious approach when developing similar transformations. Using cyclic voltammetry, density functional theory, chronopotentiometry, and Raman spectroscopy, we shed light on the causes of this issue.

Keywords

• High-throughput
• electrosynthesis
• hypervalent iodine
• phenol dearomatization