Electrochemically Driven Site-Selective C(sp2)-H Bond Hydroxylation of N-Substituted Anilines

Abstract

Organic synthesis has long been fascinated by phenolic compounds, especially their exploration of selectively hydroxylating arenes utilizing H2O as a hydroxyl source. However, phenols' low redox potential and strong reactivity frequently result in unwanted overoxidation byproducts. Here, we present an electrochemical strategy to overcome this difficulty by using electricity as an oxidant and facilitating the para-selective hydroxylation of N-protected anilines. This process exhibits excellent regio-selectivity, compatibility with diverse functional groups, and adaptability by handling an extensive range of substrates. Noteworthily, the technique provides a sustainable substitute for paracetamol synthesis and terminal acetylene-holding hydroxylated products, proving the suitability of this strategy for drug synthesis. Significantly, mechanistic investigations suggest the possible radical pathway and water as a hydroxyl source for this strategy.