The moiety of 4-imidazolidinone is an important structural motif in organic synthesis and medicinal chemistry. We achieved the efficient synthesis of 4-imidazolidinones from a variety of diamides by double Michael addition, a novel reaction mode for hypervalent alkynyl iodine compounds, and a formal reductive elimination sequence using in situ-generated EBX from TMS-EBX or EBX-MeCN. The highly reactive EBX enabled chemoselective intermolecular N- alkenylation of the sulfonamide moiety and intramolecular cyclization of the amide moiety under mild basic conditions. The reaction diastereoselectively gave cis-2,5-disubstituted 4-imidazolidinones from amino acid-derived diamides. Furthermore, 2-[(2-iodobenzoyloxy)methyl]-4-imidazolidinone was derivatized by solvolysis and Sonogashira coupling. DFT calculations indicated that the double Michael addition mechanism is plausible. Thus, the potential of an unsubstituted EBX reagent for the synthesis of heterocycles from complex molecules and their functionalization with mild nucleophiles was demonstrated.

The moiety of 4-imidazolidinone is an important structural motif in organic synthesis and medicinal chemistry. We present the synthesis of 4-imidazolidinones from various diamides with ethynyl benziodoxolones through double Michael-type addition, which is an unprecedented reaction mode for hypervalent alkynyl iodine compounds. cis-2,5-Disubstituted 4-imidazolidinones were diastereoselectively synthesized from amino acid derived diamides. Having derivatized the 4-imidazolidinones, several control experiments and density functional theory calculations were conducted to realize mechanistic insight.