Revealing the Mechanism of TEMPO-Hypervalent Iodine(III) Oxidation of Alcohols

This paper reports experimental and computational studies on the mechanism of a popular and well-known procedure for the oxidation of alcohols to carbonyl compounds using TEMPO and the hypervalent iodine reagent PIDA. Easy to obtain kinetic data shows that the mechanism, long assumed but never investigated, is unlikely to be in operation due to zero order behavior observed in TEMPO. Instead, in depth kinetic studies suggest two rate determining steps involving a combination of alcohol, hypervalent iodine species, and water, typically present in advantageous quantities and without which the reac-tion does not proceed. Studying different model alcohols suggests the mechanism to be general. Intramolecular radical trap probes rule out a radical mechanism, while an investigation of TEMPO derivatives suggests that TEMPO is involved prior to the rate determining step. Detailed kinetic isotope effect studies demonstrate that TEMPO is also involved after the rate de-termining step. Electrochemical studies find that the oxoammonium form of TEMPO is reduced by PIDA, likely oxidizing the iodine(III) to an iodine(V) species. Theoretical investigations prove the feasibility of a pathway involving an iodine(V) species, demonstrating good agreement with the experimentally derived kinetics, and support an updated mechanism