Work

Sulfonyl-PYBOX/ErCl3 complex enable highly enantioselective synthesis of α,α-dialkyl and α-alkyl-α-aryl hydrazinonitriles

Year: 2026

Type: article

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 α -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 50 = 15.11 mg∙L –1 ) was identified, rivaling commercial insecticides.

Source: Nature Communications

DOI: 10.1038/s41467-026-74600-0