Aromatization of 1,3-Cyclohexanedione: Modular Synthesis of 2,3-Disubstituted Phenols

Abstract

Multifunctional arenes play a crucial role in the chemical and pharmaceutical industries, yet their synthesis remains a significant synthetic challenge. In this study, we introduce a novel one-step strategy for the efficient synthesis of multi-substituted phenols containing hydroxy, halogen, and sulfonamido groups, all of which demonstrate notable biological activity. This work represents the first example of an aromatization-driven approach to 1,2,3-trisubstituted benzene derivatives. Remarkably, the resulting 1,2,3-trisubstituted benzene scaffold is amenable to multiple late-stage modifications, facilitating the synthesis of 1,2,3,4-tetrasubstituted benzene derivatives—compounds that are typically challenging to obtain using conventional synthetic methods. Furthermore, the method offers compatibility with diverse functional groups, it proceeds under mild reaction conditions, and it uses readily available starting materials, positioning it as a highly promising tool for pharmaceutical and materials research.