Access to Chiral Diamine Derivatives through Stereoselective Cu-Catalyzed Reductive Coupling of Imines and Allenamides

Chiral 1,2-diamino compounds are important building blocks in organic chemistry for biological applications and as asymmetric inducers in stereoselective synthesis that are challenging to prepare in a straightforward and stereoselective manner. Herein, we disclose a cost-effective and readily available Cu-catalyzed system for the reductive coupling of a chiral allenamide with N-alkyl substituted aldimines to access chiral 1,2-diamino synthons as single stereoisomers in high yields. The method shows broad reaction scope and high diastereoselectivity and can be easily scaled using standard Schlenk techniques. Mechanistic investigations by density functional theory calculations identified the mechanism and origin of stereoselectivity. In particular, the addition to the imine was shown to be reversible, which has implications toward development of catalyst-controlled stereoselective variants of the identified reductive coupling of imines and allenamides.

Automated summary

A cost-effective and readily available Cu-catalyzed system for reductive coupling of chiral allenamide with N-alkyl substituted aldimines to access chiral 1,2-diamino synthons has been disclosed in this study, providing high yields of single stereoisomers. The method shows broad reaction scope, high diastereoselectivity, and easy scalability. Mechanistic investigations have identified the reversible addition to the imine, impacting the development of catalyst-controlled stereoselective variants of the reductive coupling.