A new protocol for the synthesis of 2-quinolones from (E)-2-aminocinnamic acid derivatives has been developed, employing a thiolate as a nucleophilic promoter for cyclization. The reaction begins with conjugate addition of the thiolate to the 2-aminocinnamic acid derivatives, generating β-sulfide-substituted dihydrocinnamic acid intermediates. These intermediates can adopt conformations that bring the amino and carboxyl groups into close proximity through free rotation about the Cα–Cβ single bond. Subsequent intramolecular condensation between the amino and carboxyl groups, followed by elimination of hydrogen sulfide, furnishes the desired 2-quinolones. A broad range of 2-aminocinnamic acid derivatives are compatible with this transformation, delivering the corresponding 2-quinolone derivatives in excellent yields. Furthermore, this method is also applicable to the synthesis of all regioisomers of 2-aza-quinolones from 2-amino-aza-cinnamate derivatives. The simple operation, facile isolation of quinolones by recrystallization, and gram-scale scalability further highlight the practical utility of this protocol.
Kim et al. (Mon,) studied this question.