The reactivities were significantly lower than those in entries 1 and 2, but the reaction could be completed overnight at room temperature. The catalysts were completely dissolved in AcOH and the reaction mixture remained in the solution throughout the reaction in entries 3-5. From the viewpoint of application to pharmaceutical manufacturing, the residual amount of copper must be controlled according to ICH Q3D . Iron and zinc have low toxicity and are not listed in ICH Q3D. In comparison with the initial reaction rate of 60 min, Fe(NO3)3/TEMPO in entry 3 shows high potential for further optimization. Aerobic oxidation using transition metals instead of TEMPO was also investigated. Pd(OAc)2 (entry 6) and Cu(OAc)2 (entry 7) , and Ni(OH)2 (entry 8) left the starting material 1a. Pd(OAc)2 led to moderate conversion, but Pd(OAc)2 did not dissolve in toluene even with pyridine. As a substitute for TEMPO, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) was tried (entries 9-10) .