Remote Hydroxylation through Radical Translocation and Polar Crossover
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Mild conditions are reported for the hydroxylation of aliphatic C-H bonds through radical translocation, oxidation to carbocation, and nucleophilic trapping with H2O. This remote functionalization employs fac-[Ir(ppy)3] together with Tzo sulfonate esters and sulfonamides to facilitate the site-selective replacement of relatively inert C-H bonds with the more synthetically useful C-OH group. The hydroxylation of a range of substrates and the methoxylation of two substrates through 1,6- and 1,7-hydrogen-atom transfer are demonstrated. In addition, a synthesis of the antidepressant fluoxetine using remote hydroxylation as a key step is presented. Mild conditions have been developed for the remote functionalization of aliphatic C-H bonds through radical translocation and oxidation of the resulting radical to the carbocation as a prerequisite to nucleophilic attack. The employment of fac-[Ir(ppy)3] together with the Tzo group facilitates the site-selective replacement of inert C-H bonds with a C-OH group.
Publication Source (Journal or Book title)
Angewandte Chemie - International Edition
Hollister, K., Conner, E., Spell, M., Deveaux, K., Maneval, L., Beal, M., & Ragains, J. (2015). Remote Hydroxylation through Radical Translocation and Polar Crossover. Angewandte Chemie - International Edition, 54 (27), 7837-7841. https://doi.org/10.1002/anie.201500880