Stereospecific Epoxide‐to‐Cyclopropylamine Conversion by a Homologous Horner–Wadsworth–Emmons‐Type Reaction With an Imine‐Substituted Phosphine Oxide

We report a homologous Horner–Wadsworth–Emmons‐type reaction of an imine‐substituted phosphine oxide with epoxides, enabling a formal O‐to‐C(NH 2 ) atom swap to access structurally important cyclopropylamines. This transformation proceeds with high stereochemical fidelity, translating the chirality of epoxides into cyclopropylamines with ≥ 98% enantiospecificity, and accommodating a wide range of mono‐, 2,2‐, and 2,3‐disubstituted epoxides. The strategy's robustness is demonstrated by the efficient, scalable synthesis of the core scaffolds of bioactive molecules such as ticagrelor and tranylcypromine. DFT calculations elucidate the role of the imino group in facilitating the reaction and illustrate the origin of diastereoselectivity through a rigid, chelated transition state model.