Synthesis of α-(4-Oxazolyl)amino Esters via Brønsted Acid Catalyzed Tandem Reaction

A one-step, Brønsted acid catalyzed tandem reaction for the synthesis of α-(4-oxazolyl)amino esters was developed. 4-Nitrobenzenesulfonic acid was found to be an efficient catalyst for the coupling of ethyl 2-oxobut-3-ynoates with amides to provide various α-(4-oxazolyl)amino esters. The experimental and X-ray crystallographic data suggest that a series of bond-forming reactions including imine formation, intermolecular Michael addition, and intramolecular Michael addition are involved to generate both the oxazole and amino acid functionalities.