Novel SyntheticMethod and Insecticidal Evaluationof CF₃‑Containing Polycyclic Neonicotinoid Derivatives

The modification of active ingredients with a trifluoromethyl group represents a significant approach for the discovery of highly active pesticides. Herein, we developed a novel [3 + 3] annulation reaction of neonicotinoid precursors and trifluoromethyl-α,β-ynones and synthesized a series of CF₃-containing polycyclic neonicotinoid derivatives in high efficiency. The insecticidal activity results indicated that most of the target compounds showed good insecticidal activities against Aphis craccivora and Nilaparvata lugens at a concentration of 100 mg/L. In particular, compounds <b>3o</b> and <b>4k</b> had LC₅₀ values of 1.53 and 1.47 mg/L against A. craccivora, respectively, which were comparable to that of imidacloprid (LC₅₀ = 1.30 mg/L). The honeybee toxicity predictive model also indicated the potential low honeybee toxicity of target compounds <b>3o</b> and <b>4k</b>. The molecular docking study revealed that the target compounds <b>3o</b> and <b>4k</b> exhibited a favorable binding mode with the Lymnaea stagnalis acetylcholine-binding protein and the R55T-mutated resistant model.