Aerobic oxidations catalyzed by N-hydroxyphthalimide (NHPI) are commonly utilized for the oxygenation of activated C–H bonds (allylic, benzylic, adjacent to heteroatoms).
[i] NHPI undergoes proton-coupled oxidation to afford phthalimido-
N-oxyl (PINO), which then mediates HAT from weak C–H bonds. In 1983, prior to the development of aerobic methods to generate PINO, Masui and co-workers demonstrated the ability to access PINO from NHPI under electrochemical conditions
[ii] and site-selective oxygenation of the electrochemically generated radical using O
2 as radical trap.
[iii] Electrochemical PINO generation was utilized recently for scalable oxidation of terpenes
[iv] and benzylic oxygenation of heterocyclic compounds.
[v] In the latter reactions, metal-free electrochemical oxygenation overcomes the challenges encountered with chelating substrates that inhibit Co/NHPI-catalyzed aerobic oxidation reactions. Electrochemical oxidation of NHPI to PINO additionally presents the opportunity to trap organic radicals with reagents other than
O-atom sources. This presentation will describe the first example of this concept, showing that iodine (I
2) is an effective radical trap for electrochemical NHPI-mediated oxidation of methylarenes to benzyl iodides.
The method provides the basis for direct (in situ) or sequential benzylation of diverse nucleophiles using methylarenes as the alkylating agent. Voltammetric studies demonstrate that this mediated HAT mechanism for C–H iodination allows C–H oxidation to proceed with minimal dependence on the substrate electronic properties, contrasting benzylic C–H functionalization methods that proceed via direct electron transfer. The operating potential of the NPHI-mediated process is 0.5 – 1.2 V lower than that of direct electrochemical C–H oxidation.
[i]. Recupero, F.; Punta, C. Chem. Rev. 2007, 107, 3800.
[ii]. Masui, M; Hara, S.; Ueshima, T.; Kawaguchi, T.; Ozaki, S. Chem. Pharm. Bull. 1983, 31, 4209.
[iii]. Masui, M.; Hosomi, K.; Tsuchida, K.; Ozaki, S. Chem. Pharm. Bull. 1985, 33, 4798.
[iv]. Horn, E. J.; Rosen, B. R.; Chen, Y.; Tang, J.; Chen, K.; Eastgate, M. D.; Baran, P. S. Nature 2016, 533, 77.
[v]. Hruszkewycz, D. P.; Miles, K. C.; Thiel, O. R.; Stahl, S. S. Chem. Sci. 2017, 8, 1282.
