Accessing Rare Α-Heterocyclic Aziridines Via Brønsted Acid-catalyzed Michael Addition/Annulation: Scope, Limitations, and Mechanism.

We report an approach to the diastereoselective synthesis of 1,2-disubstituted heterocyclic aziridines. A Bronsted acid-catalyzed conjugate addition of anilines to trisubstituted heterocyclic chloroalkenes provides an intermediate 1,2-chloroamine. Diastereocontrol was found to vary significantly with solvent selection, with computational modelling confirming selective, spontaneous fragmentation in the presence of trace acids, proceeding through a pseudo-cyclic, protonated intermediate and transition state. These chloroamines can then be converted to the aziridine by treatment with LiHMDS with high stereochemical fidelity. This solvent-induced stereochemical enrichment thereby enables an efficient route to rare cis-aziridines with high dr. The scope, limitations, and mechanistic origins of selectivity are also presented. We report an approach to the diastereoselective synthesis of rare 1,2-disubstituted heterocyclic aziridines. Our approach utilizes an inherent degradation of 1,2-chloroamines in the presence of trace acid, followed by annulation to give a diverse array of cis-aziridines which are not captured by alternative synthetic methodologies. The scope, limitations, and mechanistic insights into the selectivity are presented. image