Asymmetric Transfer Hydrogenation of Stable NH Imines for the Synthesis of Enantiopure α-Chiral Primary Amines

Although it offers a direct route to access synthetically valuable alpha-chiral primary amines, asymmetric transfer hydrogenation of NH imines has been rarely studied, due in large part to the inaccessibility and instability of NH imines. Herein, we report a Rh-catalyzed asymmetric transfer hydrogenation of a kind of novel and stable NH imines which are prepared via condensation of easily available sulfonylated 2'-aminoacetophenones with NH3 in methanol. With this method, enantioenriched chiral 2-(1-aminoalkyl)anilines, which are privileged pharmacore groups, have been synthesized with good functional group compatibility, and with up to 99% ee. A gram-scale reaction using 0.2 mol% of catalyst has been successfully performed to highlight the practicality. Furthermore, the products can be derivatized into enantiopure bioactive molecules as well as chiral tridentate ligands for metal catalysis.