Synthesis of Imidazolidinone, Imidazolone, and Benzimidazolone Derivatives through Oxidation Using Copper and Air Dazhi Li, and Thierry Ollevier* Département de chimie, Université Laval, 1045 avenue de la Médecine, Québec, QC, G1V 0A6, Canada Supporting Information Placeholder ABSTRACT: A new synthetic method of urea derivatives using copper and air was developed. These mild conditions provided moderate to very good yields for 15 examples (53–93%), while low yields were obtained with sterically hindered substrates (3 examples). The reaction was found to go through an in situ-generated copper-N-heterocyclic carbene, which is then oxidized into cyclic urea derivatives possessing alkyl, benzyl, aryl, hydroxy, Boc-protected, and tertiary amine groups. Urea derivatives play an important role in medicinal chemistry, 1, 2 as they show many biological and pharmacological activities, e.g. cofactor Biotin, 3 Kealiiquinone from Micronesian sponge, 4 antago- nist Naamidine A, 5 and cytotoxin Agelastatin A (Figure 1). 6 Among urea derivatives, imidazolidinones and benzimidazolones are two important categories, e.g, antiviral agent DBPR103 7 and RSV inhib- itor BMS-433771 (Figure 1). 8-10 For this reason, new approaches for the synthesis of urea derivatives remain of interest. 2, 11 In the course of our studies towards the synthesis of various copper-N- heterocyclic carbene complexes (Cu-NHC) from imidazolinium and benzimidazolium derivatives, the corresponding urea deriva- tives were advantageously isolated instead of the expected Cu- NHCs. We disclose herein a new synthetic method to prepare these ureas. Figure 1. Structures of Selected Biologically Active Urea Derivatives. Among the previously described synthetic methods, the oxida- tion of imidazolium, imidazolinium, and benzimidazolium sub- strates into urea derivatives has been disclosed, using strong oxi- dants, such as PhI(OAc)2, 12 NaOCl, 13-15 di-tert-butyl peroxide, 16 H2O2, 17, 18 and m-chloroperoxybenzoic acid (m-CPBA) (Scheme 1). 19, 20 A major disadvantage of using strong oxidants is their in- compatibility with oxidant-sensitive functionalities, thus hindering the substrate scope. Here, we would like to report mild, easy, and practical conditions using copper metal and air for the oxidation of imidazolium, imidazolinium, and benzimidazolium substrates to obtain the corresponding urea derivatives. The conditions are applicable to substrates bearing alkyl, benzyl, aryl, primary hydroxy, acid-sensitive tert-butyloxycarbonyl group (–Boc), and tertiary amine groups. Scheme 1. Synthesis of Urea Derivatives by Oxidation