Synthesis of 2‑Quinolones via Thiolate-Mediated Cyclization of (E)‑2-Aminocinnamic Acid Derivatives.

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.