Modular Synthesis of Enantioenriched α-Chiral Homoallylic Amidines Enabled by Relay Ir/Cu Catalysis

Abstract

The cascade of Ir-catalyzed enantioselective allylic amination and Cu-catalyzed alkyne–azide cycloaddition was designed for the asymmetric synthesis of homoallylic amidines. The nucleophilic addition of an in situ-generated enantioenriched tertiary allylamine to a ketenimine intermediate triggers a rapid and stereospecific zwitterionic aza-Claisen rearrangement in a 1,3-chiral transfer manner. The approach allows modular access to enantioenriched α-chiral homoallylic amidines in high yields with a high level of enantiomeric purity.

Chemoselectivity of the CuAAC/Ring Cleavage/Cyclization Reaction between Enaminones and α-Acylketenimine

“…Until now, the ketenimides are mainly generated by amides, isonitriles, or ynamides . And the most efficient method is the copper-catalyzed sulfonyl azide–alkyne cycloaddition/ring cleavage (CuAAC/ring cleavage reaction), which can generate ketenimides in situ and be applied to synthesize numerous N -containing and N -containing heterocyclic compounds …”