Controlling Selectivity in Aliphatic C−H Oxidation through Supramolecular Recognition

Abstract

Aliphatic C-H oxidation is the most straightforward approach to functionalize hydrocarbon skeletons. The main challenge of this reaction is the control of site selectivity, given the multiple C-H bonds present in any organic molecule. Natural enzymes elegantly solve this problem through the interplay of different interactions that geometrically orient the substrate to expose a single C-H bond to the active unit, thus overriding intrinsic reactivity patterns. A combination of molecular catalysts and supramolecular receptors can be a promising way to replicate such control. This strategy indeed unlocks hydroxylation of C-H bonds that are not accessible with conventional methodologies, in which the selectivity is dictated by the geometry of the substrate-receptor adduct. Herein, we review the reports of recognition-driven C-H oxidation reactions and highlight the key design principles that inspired these works.

Copper‐Coordinated Histidyl Bolaamphiphile Assembly as an Oxidative Catalyst: Coordination Structure and Catalytic Activity in Cyclohexane Oxidation

“…Hydroxylation is an oxidation process wherein a CÀ H bond in a hydrocarbon is oxidized to form CÀ OH. [12,13] For cyclohexane hydroxylation to form cyclohexanol, which is required in the production of nylon, [14,15] oxidative supramolecular catalysts have been examined. For example, metalloporphyrin-based homogeneous catalysts mimicking the active site of cytochrome P450 have been studied for cyclohexane oxidation, [16][17][18] and their immobilization on a solid support via covalent bonding has been investigated in recent decades.…”

Continued Progress towards Efficient Functionalization of Natural and Non‐natural Targets under Mild Conditions: Oxygenation by C−H Bond Activation with Dioxirane

“…Cyclodextrins (CDs) provide promising supramolecular control for selectiveC ÀHb ond oxidation in water by using dioxirane generatedi ns itu. [84] For example, in 2012, Wong and co-workers described the site-selective CÀHb ond hydroxylationo f esters by dioxirane generated in situ in aqueous medium (Scheme 26). [85] In the presence of CDs, 60 underwent site-selective CÀH bond oxidation with TFDO in water to deliver 61 and 62 as the hydroxylation products to two tertiaryC ÀHb onds (Scheme26).…”

“…The host-guest inclusion complexes are able to preventt he approacho fd ioxiranet ot he CÀHb onds inside the cavity. [84,85] Thereby,t his site-selective CÀHb ond oxidation is the result of the highers teric hindrance induced to someC ÀHb onds throughi nclusion complexation with cyclodextrins. [84,85] In 2017, the same research group extended this approach to the hydroxylation of cis-a nd trans-substituted cyclohexanes in the presence of CDs by using dioxirane generated in situ from TFP and oxone in aqueous medium.…”

“…[84,85] Thereby,t his site-selective CÀHb ond oxidation is the result of the highers teric hindrance induced to someC ÀHb onds throughi nclusion complexation with cyclodextrins. [84,85] In 2017, the same research group extended this approach to the hydroxylation of cis-a nd trans-substituted cyclohexanes in the presence of CDs by using dioxirane generated in situ from TFP and oxone in aqueous medium. [86] As shown in Scheme 27, trans-1,4-dimethylcyclohexane can be oxidized by dioxirane generated in situ through complexation with g-CD or b-CD in mono-a nd dihydroxylated products, whereas cis-1,2-dimethylcyclohexane gave only monohydroxylation.…”

Lichtgetriebene Ein‐Elektronen‐Transferprozesse als Funktionsprinzip in der Schwefel‐ und Selen‐Multikatalyse

“…[12] Eine besondere Herausforderung,die im direkten Zusammenhang mit der direkten Funktionalisierung von nicht-aktivierten Element-Wasserstoff-Bindungen (E À H; E = B, C, N, O) in organischen Molekülen steht, ist die Kontrolle über die Regioselektivität. [13] Einer der prominentesten Lçsungsansätze fürd ieses Problem ist die Nutzung von Lewis-basischen Gruppen innerhalb der Edukte,d ie als dirigierende Einheiten die Reaktivitäte ntsprechender Katalysatoren çrtlich steuern. Alternativ werden zuweilen auch physikochemische Unterschiede zwischen den verschiedenen Element-Wasserstoff-Bindungen ausgenutzt (z.…”