Synthesis of chiral anti-1,2-diamine derivatives through copper(I)-catalyzed asymmetric \u03b1-addition of ketimines to aldimines

Xu-Cheng Gan,Cheng-Yuan Zhang,Liang Yin,Feng Zhong,Ping Tian

doi:10.1038/s41467-020-18235-9

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.

Highlights

Chiral 1,2-diamines serve as common structure units in bioactive molecules and useful ligands for a range of catalytic asymmetric reactions
We show the catalytic asymmetric α-addition of ketimines derived from trifluoroacetophenone and 2- or 4-NO2benzylamines to aldimines, which furnishes a series of anti-1,2diamine derivatives in moderate-to-high yields with moderate-tohigh diastereoselectivity and high-to-excellent enantioselectivity
The reaction between ketimine 1a and N-Boc-aldimine 2a was performed in the presence of 5 mol % Cu(CH3CN)4PF6, 5 mol % (R)-BINAP, and 5 mol % Barton’s Base (Table 1, entry 1)

Summary

Introduction

Chiral 1,2-diamines serve as common structure units in bioactive molecules and useful ligands for a range of catalytic asymmetric reactions. 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. Chiral 1,2-diamines have been identified as one of the most important structural motifs in bioactive natural products and pharmaceutical compounds[1,2,3,4]. Chiral 1,2-diamines have been identified as one of the most important structural motifs in bioactive natural products and pharmaceutical compounds[1,2,3,4] They served as both powerful ligands in transition metal-catalyzed asymmetric reaction and efficient chiral organocatalysts[5,6,7,8]. By changing the electronic property on the ligand (FOXAP), both syn- and anti-

Methods

Results

Conclusion