Synthesis of Oxazoles from Alkyl Aryl Ketones and Nitriles Using Oxone

Significance

The reaction of nitriles with alkyl aryl ketones in the presence of iodoarenes under conditions of Oxone and TfOH to afford 2,5-di- and 2,4,5-trisubstituted oxazoles is reported. Under these conditions the desired products were prepared in one pot. Of significance is the fact that metal-free conditions are used involving in situ derived hypervalent iodonium intermediates from the reaction of Oxone with iodoarenes. This aryliodonium species reacts with the enolate of the ketone to generate the corresponding β-keto iodonium intermediate. Iodobenzene and 4-chloroiodobenzene gave the best yields. For nitrile substrates, R^¹= Me afforded the highest product yields. For the alkyl aryl ketones, both electron-rich and electron-deficient aromatics led to moderate yields of oxazoles. A possible mechanism for the reaction was proposed.