Synthesis of 4‐Alkoxy‐1,3‐oxazol‐5(2H)‐ones, Precursors of 1‐alkoxy substituted nitrile ylides

Abstract 4‐Alkoxy‐1,3‐oxazol‐5(2H)‐ones of type 4 and 7 were synthesized by two different methods: oxidation of the 4‐(phenylthio)‐1,3‐oxazol‐5(2H)‐one 2a with m‐chloroperbenzoic acid in the presence of an alcohol gave the corresponding 4‐alkoxy derivatives 4, presumably via nucleophilic substitution of an intermediate sulfoxide (Scheme 2). The second approach is the BF3‐catalyzed condensation of imino‐acetates of type 6 and ketones (Scheme 3). The yields of this more straightforward method were modest due to the competitive formation of 1,3,5‐triazine tricarboxylate 8. At 155°, 1,3‐oxazol‐5(2H)‐one 7b underwent decarboxylation leading to an alkoxy‐substituted nitrile ylide which was trapped in a 1,3‐dipolar cycloaddition by trifluoro‐acetophenone to give the dihydro‐oxazoles cis‐ and trans‐9 (Scheme 4). In the absence of a dipolarophile, 1,5‐dipolar cyclization of the intermediate nitrile ylide yielded isoindole derivatives 10 (Schemes 4 and 5).