Synthesis of chiral anti-1,2-diamine derivatives through copper(I)-catalyzed asymmetric α-addition of ketimines to aldimines.

ABSTRACT

Chiral 1,2-diamines serve as not only common structure units in bioactive molecules but also useful ligands for a range of catalytic asymmetric reactions. Here, we report a method to access anti-1,2-diamine derivatives. By means of the electron-withdrawing nature of 2- or 4-nitro-phenyl group, a copper(I)-catalyzed asymmetric α-addition of ketimines derived from trifluoroacetophenone and 2- or 4-NO2-benzylamines to aldimines is achieved, which affords a series of chiral anti-1,2-diamine derivatives in moderate to high yields with moderate to high diastereoselectivity and high to excellent enantioselectivity. Aromatic aldimines, heteroaromatic aldimines, and aliphatic aldimines serve as suitable substrates. The nitro group is demonstrated as a synthetical handle by several transformations, including a particularly interesting Fe(acac)3-catalyzed radical hydroamination with a trisubstituted olefin. Moreover, the aryl amine moiety obtained by the reduction of the nitro group serves as a synthetically versatile group, which leads to the generation of several functional groups by the powerful Sandmeyer reaction, such as -OH, -Br, -CF3, and -BPin.