A Controlled Cyclization of Functionalized Thioureas and Unprecedented Termolecular Decyclization of Iminothiazolidinones

Abstract

AbstractA series of thiourea derivatives bearing pendant hydroxyl groups was synthesized. These quadruply nucleophilic compounds underwent cyclization reactions with bromoacyl bromides, yielding two isomeric iminothiozolidinones. While the remote hydroxyl group in functionalized thioureas was not directly involved in the cyclization, it allowed us to establish control over the product formation through the choice of temperature and/or solvent. The new mode of temperature‐dependent control over the product distribution was different from the classical kinetic vs thermodynamic control. A number of synthesized iminothiozolidinones underwent an unprecedented termolecular decyclization reaction in the presence of an external nucleophile and a proton to yield aminooxoethylcarbamothionates. In addition to the theoretical importance of this newly discovered reaction, there is also a practical need for these decyclized products as they are known privileged structures in the family of HIV‐1 transcriptase inhibitors.