Polyfunctionalized arenes, prized for their versatile structural properties, pose challenges in synthesis due to the stepwise modification required, often involving costly noble metal catalysts and suffering from low reactivity and selectivity.  

In a study published in Science Advances, the research group led by Prof. SU Weiping and Prof. JIE Xiaoming from Fujian Institute of Research on the Structure of Matter of the Chinese Academy of Sciences reported dehydrogenative synthesis of N-functionalized 2-aminophenols from cyclohexanones and amines. 

Researchers found that the synthesis of N-functionalized 2-aminophenols could be achieved under transition-metal-free conditions. By leveraging inexpensive 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) as a mild oxidant, they incorporated amino and hydroxyl groups into aromatic rings in a single step, simplifying the synthesis process remarkably. 

This streamlined synthesis route has several advantages. Notably, it enables the production of N-functionalized 2-aminophenols from readily available cyclohexanones and primary amines in good-to-excellent yields, presenting a concise way to precursors of valuable natural products such as carbazole alkaloids. Moreover, its applicability extends to the late-stage modification of complex natural products and pharmaceuticals. 

One intriguing finding is the identification of water's crucial role in protecting aliphatic amine moieties from over-oxidation. The in-situ generation of water from ketone-amine condensation serves to alleviate electron density in the amine portion, impeding the interaction of TEMPO with vulnerable 2-aminophenol products. This not only enhances the selectivity of the synthetic process but also holds promise for advancing highly selective methodologies in the field. 

This study paves the way for the development of more efficient protocols for generating polyfunctionalized arenes.