Thiolate-mediated cyclization yields 2-quinolones efficiently

What the study found: A new protocol was developed to synthesize 2-quinolones from (E)-2-aminocinnamic acid derivatives using a thiolate as a nucleophilic promoter for cyclization. The abstract also states that the method works for making all regioisomers of 2-aza-quinolones from 2-amino-aza-cinnamate derivatives.
Why the authors say this matters: The authors say the protocol is practically useful because it is simple to operate, allows quinolones to be isolated easily by recrystallization, and can be scaled to gram quantities.
What the researchers tested: The researchers tested thiolate-mediated cyclization of (E)-2-aminocinnamic acid derivatives. In the described sequence, thiolate adds in a conjugate addition step, the resulting intermediates cyclize intramolecularly, and hydrogen sulfide is eliminated to form 2-quinolones.
What worked and what didn't: A broad range of 2-aminocinnamic acid derivatives were compatible with the transformation, and the corresponding 2-quinolone derivatives were obtained in excellent yields. The method also applied to 2-amino-aza-cinnamate derivatives, producing all regioisomers of 2-aza-quinolones.
What to keep in mind: The abstract does not describe failures, side reactions, or specific substrate limits. No detailed limitations are given in the available summary.

Key points

• A thiolate-promoted protocol was developed for making 2-quinolones from (E)-2-aminocinnamic acid derivatives.
• The reaction proceeds through thiolate addition, intramolecular condensation, and elimination of hydrogen sulfide.
• A broad range of starting materials was compatible, and the products were obtained in excellent yields.
• The method also worked for 2-amino-aza-cinnamate derivatives, giving all regioisomers of 2-aza-quinolones.
• The authors describe the procedure as simple, easy to purify by recrystallization, and scalable to gram size.