Synthesis of 2?Phenyl-4,5-Substituted Oxazoles by Copper-Catalyzed Intramolecular Cyclization of Functionalized Enamides

摘要

An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving intramolecular copper-catalyzedncyclization of highly functionalized novel β-(methylthio)enamides as the key step has been reported. These enamides arenobtained by nucleophilic ring-opening of newly synthesized 4-[(methylthio)hetero(aryl)methylene]-2-phenyl-5-oxazolonenprecursors by alkoxides, amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the introduction of an ester,nN-substituted carboxamide or acyl functionalities at 4-position of the product oxazoles. Synthesis of two naturally occurring 2,5-ndiaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis−decarboxylation of the corresponding 2,5-diaryloxazole-n4-carboxylates has also been described. Similarly, three of the serine-derived oxazole-4-carboxamides were elaborated to novelntrisubstituted 4,2′-bisoxazoles through DAST/DBU-mediated cyclodehydration−dehydrohalogenation sequence. The presentnprotocol is complementary and an improvement to our previously reported silver carbonate-induced cyclization of β-nbis(methylthio)enamides to 2-phenyl-5-(methylthio)-4-substituted oxazoles.