Borane‐Catalyzed Chemo‐ and Regioselective Ring Opening of 2‐Substituted Aziridines with Phenols for Direct Synthesis of β‐Arylethylamines

A metal‐free chemo‐ and regioselective nucleophilic ring opening of 2‐substituted aziridines with ortho ‐C(sp 2 ) atom of phenols enables facile access to medicinally relevant β ‐arylethylamine derivatives. In this approach, phenols act as aryl nucleophiles that favor CC bond formation selectively at the ortho ‐C(sp 2 ) position with the more substituted carbon of aziridines to generate branched, selective arylated products. Despite the significant advancement of transition‐metal‐catalyzed cross‐coupling and nucleophilic ring opening of 2‐substituted azirines, only linear arylated products are widely demonstrated. The first metal‐free branched selective nucleophilic ring opening of 2‐alkyl and 2‐aryl aziridines with phenols is reported to address this challenge. Furthermore, the diversity of the substrate scope by using N‐heterocycles as nucleophiles empowers the generation of β ‐heteroarylethylamine derivatives. A combination of computational and experimental investigation reveals that the reaction proceeds via a borane‐promoted proton transfer, followed by aziridine ring opening and Fridel–Crafts alkylation involving a π ‐complex of carbocation‐anion ion pair. This protocol is further applicable for the synthesis of pharmaceutically relevant compounds like serotonin and tryptamine.