Diazo Strategy for the Synthesis of Functionalized Naphtho[2,1-d]oxazoles

The (oxazol-4-yl)-substituted 2-diazo-1,3-dicarbonyl compounds were synthesized by azirine ring expansions of alkyl 2-diazo-3-oxo-3-(2H-azirin-2-yl)propanoates with trifluoroacetic anhydride (TFAA). The resulting alkyl 2-diazo-3-oxo-((5-aryl/hetaryl-2-trifluoromethyl)oxazol-4-yl)propanoates undergo a Rh(II)-catalyzed transformation into 4-hydroxynaphtho[2,1-d]oxazole-5-carboxylic esters by formal insertion of the metallocarbene into the aromatic C-H bond. The reaction proceeds efficiently and selectively with the vicinal unsubstituted, 2/3/4-monosubstituted, and 3,4-disubstituted benzene rings as well as with the 2-thienyl ring in the diazo substrate. The substituent in the 4-position of alkyl 4-hydroxynaphtho[2,1-d]oxazole-5-carboxylates can be easily changed by converting the OH group into a triflate and its subsequent cross-coupling reactions with high yields. The Lewis-acid-promoted cyclization of the Sonogashira cross-coupling product opens the way to 7H-benzo[7,8]isochromeno[5,6-d]oxazol-7-one derivatives with a new heterocyclic skeleton.