A Mild, Efficient Approach for the Synthesis of 1,5-Disubstituted Hydantoins

An efficient and straightforward twostep procedure for the synthesis of N1 alkylarylsubstituted hydantoins was developed, starting from easily available starting materials. The procedure envisages a highly regiospecific domino condensationazaMichael nucleophilic substitutionO→N acyl migration between activated α,βunsaturated carboxylic acids or αhaloaryl acetic acids, respectively, and Ntertbutyl or Ntritylcarbodiimides, leading to the regioselective formation of hydantoins bearing the tertiary alkylic substituent in the 3position, followed by selective removal the substituent. This process avoids the use of harsh reaction conditions and toxic reagents and is high yielding. A detailed study of the influence of the structure of the reactants on the reaction outcome is presented. A wide variety of final products having a primary, secondary, cyclic and aryl substituent at the N1 position were successfully synthesized by this method. © WileyVCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009