Enantioselective synthesis of methyl 2-[1-[(tert-butoxycarbonyl)amino]ethyl]-4-methyloxazole-5-carboxylate by a one–pot enamide cyclization

Methyl 2-1-(tert-butoxycarbonyl)amino]ethyl]-4-methyloxazole-5-carboxylate (1) was synthesized with high optical purity via a Pd–catalyzed amide coupling with vinyl triflate with subsequent oxazole formation. The latter reaction proceeds via bromination of an enamide with NBS and DBU-promoted cyclization. The oxazole subunit positional isomer in a macrocyclic azole peptide was obtained in a good yield without racemization. The scope and limitations of this reaction were also investigated.