Enantio‐ and Regioselective Construction of 1,4‐Diamines via Cascade Hydroamination of Methylene Cyclopropanes

Abstract Despite the widespread existence of chiral 1,4‐diamines in bioactive molecules and their applications in asymmetric catalysis, the catalytic and asymmetric synthesis of such structures from readily accessible substrates remains a long‐standing challenge. Here, we report a Cu‐catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4‐diamine derivatives in high yields with excellent enatioselectivities (up to 95 % yield and up to >99 % ee). The use of two hydroxylamine esters containing different functionalized amino groups allowed us to increase the complexity of the final 1,4‐diamine structures. The desired products could be easily transformed into chiral 1,4‐diamines and chiral NH 2 ‐Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring‐opening and cascade hydroamination sequence.