Oxoammonium-catalyzed oxidation

Oxoammonium-catalyzed oxidation reactions involve the conversion of organic substrates to more highly oxidized materials through the action of an N-oxoammonium species. Nitroxides may also be used in catalytic amounts in the presence of a stoichiometric amount of a terminal oxidant.

The first discovery of a stable nitroxide radical was made in 1959. Since then, they have been developed as a versatile class of organic oxidants, both in the stoichiometric and catalytic mode. A single-electron oxidation of the nitroxide radical produces a highly electrophilic oxoammonium species, which serves as the active oxidizing agent. Although pre-formed N-oxoammonium salts may be used stoichiometrically for oxidations, these have largely been replaced by catalytic methods that use a cheaper terminal oxidant, such as sodium hypochlorite or bis(acetoxy)iodobenzene (BAIB). Nitroxide radical species used are either 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or derivatives thereof. Examples of oxoammonium-based oxidations are shown below.

(1)

The mechanism of oxidation by N-oxoammonium salts is complicated by the highly electrophilic nature of both the N and O atoms in the oxoammonium group. The reaction occurs by two distinct pathways, depending on the pH of the medium.

Under neutral or slightly acidic conditions (in the presence of silica gel, for instance), oxidation occurs by an initial hydrogen bond between the hydroxyl group and the oxoammonium nitrogen, followed by simultaneous proton transfer and hydride abstraction. The need for hydrogen bonding is supported by the low reactivity of β-alkoxy and β-amino alcohols, which exhibit competitive intramolecular hydrogen bonding. The mechanism of oxidation under weakly basic (pyridine) conditions is similar, except that pyridine neutralizes the hydroxyammonium species, and this intermediate "comproportionates" with oxoammonium salt to give nitroxide radicals and pyridinium salts (see equation (3) below). Because this reaction consumes base and active oxidant, two equivalents of base and oxidant are necessary under weakly basic conditions. A unified mechanism under neutral and basic conditions in presented in a recent article. The authors present a comprehensive analysis of a number of oxoammonium salt mediated oxidations.

(2)

Under strongly basic conditions, the deprotonated substrate reacts with the N-oxyammonium species. Attack of the substrate alkoxide on either nitrogen or oxygen may occur, although the former is believed to operate on the basis of on observations of oxidations of N-alkoxy amines (which, presumably, proceed via intermediate 1). Comproportionation of the reduced product (a hydroxylamine) with the oxoammonium ion competes with oxidation; thus, an excess of the oxidizing agent is often required.

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