Synthesis of Highly Substituted Imidazolidine-2,4-dione (Hydantoin) through Tf2O-Mediated Dual Activation of Boc-Protected Dipeptidyl Compounds

Highly substituted chiral hydantoins were readily synthesized from simple dipeptides in a single step under mild conditions. This reaction proceeded through the dual activation of an amide and a tert-butyloxycarbonyl (Boc) protecting group by Tf2O-pyridine. This method was successfully applied in the preparation of a variety of biologically active compounds, including drug analogs and natural products.