Benzoxazole and Benzothiazole Synthesis from Carboxylic Acids in Solution and on Resin by Using Ethyl 2‐Cyano‐2‐(2‐nitrobenzenesulfonyloxyimino)acetate and para‐Toluenesulfonic Acid

Abstract

AbstractA metal‐free and catalytic method for the synthesis of 2‐substituted benzoxazoles and benzothiazoles from N‐protected amino acids and carboxylic acids is described. The synthesis of benzoxazole on a solid support is demonstrated by the synthesis of benzoxazole attached to a human islet amyloid polypeptide, hIAPP22–27, fragment and benzoxazole derivatives of the side chain of aspartic acid on a modified fragment of Aβ18−21 (amyloid β) peptide. The reactions proceeded through a two‐step mechanism. The coupling step is realized with a relatively new reagent, ethyl 2‐cyano‐2‐(2‐nitrobenzenesulfonyloxyimino)acetate (ortho‐NosylOXY), and the cyclization step takes place thanks to an inexpensive organocatalyst, para‐toluenesulfonic acid, under microwave irradiation. To the best of our knowledge, this is the first report of the complete synthesis of benzoxazole derivatives of a polypeptide on a resin solid support.