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

초록

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 beta-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 C alpha-C beta 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.

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