Conformational Rigidity Controlled Copper Catalyzed Chemo-divergent Annulation

The conformational rigidity of substrates is critical in determining reaction outcomes, impacting both reactivity and product selectivity. The impact of conformational rigidity in mechanistic divergence is an area that remains underexplored. In this study, we present a straightforward Cu/PhPyBox-catalyzed chemodivergent annulation reaction, wherein the rigidity of α-aminoketones dictates a switch in mechanism under identical reaction conditions. Mechanistically, hydrogen bonding inter-actions are critical to suppress the nucleophilicity of the amine, facilitating the formation of a common enaminal intermedi-ate from cyclic ethynylethylene carbonates (EEC) derived allenal, instead of propargylic substitution. This unified strategy offers access to three distinct classes of valuable nitrogenous heterocycles which are prevalent in bioactive molecules. Among these variety, indolinone derivatives exhibit significant antibacterial activity compared to the marketed drug ampicillin against multidrug-resistant gram-negative Pseudomonas aeruginosa bacteria, highlighting their potential as a source of new therapeutic agents.