Enantioselective Ugi and Ugi-azide reactions catalyzed by anionic stereogenic-at-cobalt(III) complexes

Ugi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous heterocycles. The development of structurally diverse range of novel catalytic systems and the discovery of new approaches to accommodate a broader scope of terminating reagents for asymmetric Ugi four-component reaction is still in high demand. Here, we report a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions employing anionic stereogenic-at-cobalt(III) complexes as catalysts. The key nitrilium intermediates, generated through the nucleophilic addition of isocyanides to the chiral ion-pair which consists of stereogenic-at-cobalt(III) complexes counteranion and a protonated iminium, are trapped by either carboxylic acids or in situ-generated hydrazoic acid, delivering alpha-acylamino amides and alpha-aminotetrazoles in good to excellent enantioselectivities (up to 99:1 e.r.). Ugi reactions are well known multicomponent reactions that allow the preparation of a variety of chemical compounds including peptides, heterocyclic compounds, or natural products. Here, the authors report enantioselective Ugi reactions that enable the synthesis of chiral alpha-acylamino amides and alpha-aminotetrazoles catalyzed by stereogenic-at-cobalt(III) complexes.

Automated summary

This article reports on a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions using anionic stereogenic-at-cobalt(III) complexes as catalysts. By controlling the generation and trapping of key nitrilium intermediates, highly enantioselective alpha-acylamino amides and alpha-aminotetrazoles can be obtained.