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

Despite the widespread existence of chiral 1,4-diaminesin 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 enatio-selectivities (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 NH2-Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring-opening and cascade hydroamination-sequence.