Leveraging the Domino Skeletal Expansion of Thia-/Selenazolidinones via Nitrogen-Atom Transfer in Hexafluoro­isopropanol: Room Temperature Access to Six-Membered S/Se,N-Heterocycles

Herein, a highly regioselective domino skeletal-expansion process that transforms 2-amino­thiazolidinone into six-membered S,N-heterocycle is developed with the aid of TMS-azide in hexafluoro­isopropanol (HFIP) at ambient temperature. Functioning of the C2 tertiary amine as latent reactive group on thiazolidinone moiety was the key to this development, which allowed relay substitution with azide and imparted subsequent ring-expansion under metal/acid free-conditions. The reaction also underscored an intermolecular nitrogen-atom transfer process from TMS-azide leading to final products, where any intermediary azido­thiazolidinone was absent. The strategy was extendable to analogous synthesis of Se,N-heterocycles, and furthermore, late-stage drug-modification and follow-up transformations were also performed. Density functional theory calculations and control experiments provided important mechanistic insights and highlighted potential roles of HFIP in the transformation.