Sulfonyl-PYBOX/ErCl<sub>3</sub> complex enable highly enantioselective synthesis of α,α-dialkyl and α-alkyl-α-aryl hydrazinonitriles.

Gong, Yi; Zhang, Zheng; Cao, Qiang; Wang, Cai; Jiang, Min-Chuan; Qiu, Zhi-Heng; Le, Xiao-Jing; Ye, Yu-Jie et al. · Nat Commun · 2026

basic_science · Level V

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Abstract

We report the highly enantioselective nucleophilic addition reaction of simple ketone-derived hydrazones. Accordingly, a ErCl₃-catalyzed cyanation of both aliphatic and aryl ketone hydrazones is achieved for the facile access of C<sup>α</sup>-tetrasubstituted α-hydrazino nitriles in up to 96% ee, by using the sterically confined pyridinebisoxazoline (PYBOX) ligand featuring a sulfonyl group at the pyridine C4 position. This method enables the shortest catalytic enantioselective total synthesis of L-carbidopa, a drug that could treat the symptoms of Parkinson's disease, with 82% overall yield in four steps. These adducts are valuable synthons to various α-tertiary hydrazines and related azacycles that are interesting targets for medicinal studies and pesticide research. From our biological analysis, a chiral α-hydrazino nitrile with good insecticidal activity against Aphis gossypii (LC<sub>50</sub> = 15.11 mg∙L<sup>-1</sup>) was identified, rivaling commercial insecticides.