Remote Hydroxylation through Radical Translocation and Polar Crossover

Mild conditions are reported for the hydroxylation of aliphatic C-H bonds through radical translocation, oxidation to carbocation, and nucleophilic trapping with HO. This remote functionalization employs fac-[Ir(ppy)] together with Tz 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)] together with the Tz group facilitates the site-selective replacement of inert C-H bonds with a C-OH group.