Aziridine Opening via a Phenonium Ion Enables Synthesis of Complex Phenethylamine Derivatives

Abstract

We report that the treatment of unsymmetrical 2,3-disubstituted aziridines with TiCl 4 yields β-phenethylamine products via the intermediacy of a phenonium ion. Derivatization of the products obtained via this method is demonstrated. Computational analysis of the reaction pathway provides insight into the reaction mechanism, including the selectivity of the phenonium opening.

Recent advances in the accessibility, synthetic utility, and biological applications of aziridines

“…Ring opening reactions are amongst the most important synthetic pathways of aziridines 68 as they can be transformed into many interesting compounds such as amino acids and natural products 69 that are very often useful for pharmacological applications.…”

Reductive Opening of Oxetanes Catalyzed by Frustrated Lewis Pairs: Unexpected Aryl Migration via Neighboring Group Participation

“…Further intramolecular nucleophilic attack by the well-positioned aryl group leads to phenonium ion D . Then, cyclopropane ring opening by cleavage of the other C–C forms a more stable secondary carbocation E and completes the aryl migration . Subsequent reduction by the boryl hydride anion forms the observed product 3 .…”

“…The formation of 3a is a result of double reduction with concomitant migration of the 3-aryl group. Mechanistically, we believe that the initial hydrosilylation product 4a might undergo further activation by the silylium ion, leading to the highly reactive phenonium ion IM , via which the aryl group migrates to the adjacent position (known as neighboring group participation) prior to the second reduction …”