Abstract Heterocyclic compounds are of significant importance in the fields of organic synthesis and medicinal chemistry. Current synthetic methods for these molecules often rely on specific building blocks or transition-metal catalysis, which impose certain limitations in terms of methodology. Consequently, the development of metal-free synthetic methodologies for heterocycles is of great importance. In this study, readily available and inexpensive additives, TsOH·H₂O and CH₃COOH, were employed as the mediators. By modulating the solvent system, isocoumarin and isoquinoline derivatives were efficiently synthesized in CH₃CN and DMF, respectively. Notably, this method enables a rapid and efficient synthesis of the natural product Thunberginol A under metal-free conditions. This strategy offers a practical and efficient approach for constructing relevant drug-like core skeletons.
Yue et al. (Thu,) studied this question.