Novel Synthetic Method and Insecticidal Evaluation of 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 3o and 4k 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 3o and 4k. The molecular docking study revealed that the target compounds 3o and 4k exhibited a favorable binding mode with the Lymnaea stagnalis acetylcholine-binding protein and the R55T-mutated resistant model.