Advances in Enantioselective Synthesis and Chiral Resolution of Insecticides

Chirality has emerged as a critical determinant in the design, efficacy, and environmental behavior of modern insecticides. While a significant proportion of agrochemicals are inherently chiral, most are still commercialized as racemic mixtures, despite well-documented differences in biological activity, toxicity, and degradation pathways between enantiomers. In this review, we provide a comprehensive and critical analysis of advances in the stereoselective synthesis and resolution of chiral insecticides, with particular emphasis on neonicotinoids, pyrethroids, and oxadiazines, including indoxacarb. A systematic survey of the literature (1985–2025), including peer-reviewed articles and patents, reveals that multiple strategies have been developed to access enantiomerically enriched compounds, including asymmetric organocatalysis, transition-metal catalysis, chiral-pool approaches, biocatalytic transformations, and chromatographic resolution techniques. Among these, recent developments in photoredox catalysis, recyclable metal complexes, and enzyme-mediated processes have significantly improved enantioselectivity and scalability, bridging the gap between academic methodologies and industrial applications. Despite these advances, challenges remain in achieving cost-effective, sustainable, and universally applicable asymmetric processes. Importantly, the relationship between stereochemistry and biological performance underscores the need for integrating synthetic chemistry with toxicological and environmental studies. Future directions point toward the incorporation of green chemistry principles, continuous-flow processes, and computational tools, including machine learning and molecular modeling, to accelerate the rational design of enantiopure agrochemicals. This review highlights both the progress achieved and the critical gaps that must be addressed to realize the potential of stereoselective insecticide development fully.