A Convenient Synthesis of Unsymmetrically Substituted Ureas via Carbamoyl Azides of alpha-N-Protected Amino Acids

A simple and efficient two-step synthesis of unsymmetrically substituted ureas containing an amino acid derivative is reported. The procedure involves the reaction between the carbamoyl azides of alpha-N-protected amino acids and ammonium hydroxide or a primary or a secondary amine. The reaction proved to be very fast (0.5 h) with small, highly reactive ammonium hydroxide and slower (4 h) with sterically hindered tert-butylamine. The H-1 NMR spectra of the synthesized, new, unsymmetrical ureas carried out in [D-6]DMSO suggest that the protons in the -(CH)-C-alpha-NHCONH-CH- moiety assume a trans conformation. Moreover, analysis of the mass spectra (El and ESI) revealed some interesting common features. The reported synthesis represents the first example of the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)