Palladium‐Catalyzed [2 + 2] Cycloaddition of Terminal Ynamides: Access to 3‐Aminocyclobutenones

This work presents the first successful [2 + 2] cycloaddition of terminal ynamides, enabled by a palladium catalyst, for the efficient synthesis of 3‐aminocyclobutenones under mild conditions. The reaction employs Pd(PPh 3 ) 4 at room temperature and completes within minutes, overcoming previous limitations such as narrow substrate scope and high sensitivity to hydrolysis. Broad functional group tolerance is demonstrated with various N ‐sulfonyl ynamides. This practical and scalable method provides direct access to valuable cyclobutenone scaffolds for medicinal chemistry applications.