Copper-Catalyzed Direct Oxidative C-H Amination Of Benzoxazoles With Formamides Or Secondary Amines Under Mild Conditions

Five-membered heterocycles with amine substituents are used wildly in medicine and materials. Methods to synthesize these motifs include cyclocondensation reactions, palladium-catalyzed Buchwald-Hartwig reactions and copper-catalyzed Ullmann reactions or Goldberg reactions. For all that the rapid and wide adoption of these methods are achieved, there still are many disadvantages with these methods, for example, the precursors should be prepared for cyclocondensation, for Buchwald-Hartwig reaction, the adoption in medicine is limited for the toxicity of the palladium, while the high temperature is needed in ullmann reaction. To further improve the efficiency of coupling-based approaches, great interest has recently toward to the transition-metal catalyzed C-H activation to direct amination.In view of the acidity of H atom in second position of oxazole, we study the C-H activation of the benzoxazole.In this paper, we study the reaction of benzoxazoles with formamides as nitrogen source or with secondary amines as nitrogen source, a series of benzoxazol-2-amine were synthesized under the best reaction condition. Compared to other methods, the external base is not needed and the oxygen even air was choosed to be the oxidant.Thus, a mild, efficiently and environmentally copper-catalyzed method for the direct amination of benzoxazoles was developed.