Enantioselective Ring-Closing C–H Amination of Urea Derivatives

Abstract

Summary An enantioselective intramolecular C(sp3)–H amination of N-benzoyloxyurea by using a chiral-at-metal ruthenium catalyst is reported, providing chiral 2-imidazolidinones in yields of up to 99% and with up to 99% ee. Catalyst loadings down to 0.05 mol % are feasible. Control experiments support a stepwise nitrene insertion mechanism through hydrogen atom transfer of a ruthenium nitrenoid intermediate followed by a radical recombination. Chiral 2-imidazolidinones are prevalent in bioactive compounds and can be converted to chiral vicinal diamines in a single step. The synthetic value of the new method is demonstrated for the synthesis of intermediates of the drugs levamisole and dexamisole, the bisindole alkaloids topsentine D and spongotine A, and a chiral organocatalyst.