Mechanism of the Copper/TEMPO‐Catalyzed Aerobic Oxidation of Alcohols

Abstract Identifying the mechanism of a catalytic reaction is paramount for designing new and improved catalysts. Several alternative catalytic cycles for the copper/2,2,6,6‐tetramethylpiperidine‐ N ‐oxyl (TEMPO)‐catalyzed aerobic oxidation of alcohols to the corresponding aldehydes or ketones were examined using DFT at the SMD(CH 3 CN)‐RIJCOSX‐DSD‐PBEB95/def2‐TZVP//DF‐PBE D3BJ /def2‐SVP level of theory. A catalytic cycle in which TEMPO remains coordinated to copper throughout was identified as the most likely mechanism. There are three components to the catalytic cycle: 1) hydrogen transfer from the alkoxyl ligand to coordinated TEMPO, 2) oxygen activation with formation of a peroxo complex, and 3) alcohol activation with transfer of the OH proton to the peroxo ligand. The oxidation takes place via a six‐membered intramolecular hydrogen‐transfer transition state. Importantly, this is not the rate‐determining step, which instead involves oxygen activation and/or the initial alcohol activation.