Remote Hydroxylation through Radical Translocation and Polar Crossover

Abstract

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 Tz(o) 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.

General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols

“…15 Furthermore, based on the usually selective β-hydride elimination step in the hybrid Pd-radical mechanism, 9b,12 it was anticipated that the alkenol product would be formed with high degrees of regiocontrol. Accordingly, we were eager to validate this premise on desaturation of challenging alcohol derivative 1a , which under conditions of the reported radical/cationic protocol 5b resulted in a nearly equal mixture of regioisomeric alkenols ( 2a-1 , 2a-1 ′, Scheme 2a). We were pleased to find that exposure of T 1 -tethered alcohol 1a-T 1 to our optimized 16 photocatalytic conditions resulted in γ -/ δ -desaturation product 2a in 77% yield as a single regioisomer, thus fully supporting the above hypothesis!…”

Alkyl Carbon–Carbon Bond Formation by Nickel/Photoredox Cross‐Coupling

“…Owing to the sheer volume of recent literature on transition metal/photoredox dual catalysis and the existence of several relevant reviews, [9,15] we have chosen to focus the scope of this Minireview on photoredox reactions that use C(sp 3 )r adicals to forge carbon-carbon bonds through aN icatalyzed cross-coupling cycle.P hotoredox reactions that accomplish carbon-heteroatom coupling or that employ other metals are therefore excluded. Processes that form carbon-carbon bonds through non-metal catalyzed photoredox mechanisms such as the Giese addition, [16] protoncoupled electron transfer (PCET), [17] radical/polar crossover processes, [18] the Minisci reaction, [19] or cycloadditions, [20] although useful in their own right, are also not discussed.…”

Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp3)−H Functionalization under Mild Reaction Conditions

“…Based on mechanistic investigations above,w ep ropose that fac-[Ir(ppy) 3 ]i sp hotoexcited to fac-[Ir(ppy) 3 ]* and reduced by the Hantzsch ester to Ir II (Scheme 3). [25] The resulting Ir II intermediate reduces the N-alkoxyphthalimide…”