Organocatalytic Oxidations Mediated by Nitroxyl Radicals

Abstract

The use of nitroxyl radicals, alone or in combination with transition metals, as catalysts in oxidation processes is reviewed from both a synthetic and a mechanistic viewpoint. Two extremes of reactivity can be distinguished: stable (persistent) dialkylnitroxyls, such as the archetypal TEMPO, and reactive diacylnitroxyls, derived from N-hydroxy imides, such as N-hydroxyphthalimide (NHPI). The different types of reactivity observed are rationalized by considering the bond dissociation energies (BDEs) of the respective N-hydroxy precursors, substrates and reaction intermediates. Reactive diacylnitroxyl radicals are generated in situ from the corresponding N-hydroxy compound. The protagonist, NHPI, catalyzes a wide variety of free radical autoxidations, improving both activities and selectivities by increasing the rate of chain propagation and/or decreasing the rate of chain termination. In the absence of metal co-catalysts improved conversions and selectivities are obtained in the autoxidation of hydrocarbons to the corresponding alkyl hydroperoxides. For example, cyclohexylbenzene afforded the 1-hydroperoxide in 97.6% selectivity at 32% conversion when the autoxidation was performed in the presence of 0.5 mol % NHPI, and the product hydroperoxide as initiator, at 100 8C. This forms the basis for a potential coproduct-free route from benzene to phenol. In combination with transition metal co-catalysts, notably cobalt, NHPI and related compounds, such as N-hydroxysaccharin NHS, afford effective catalytic systems for the effective autoxidation of hydrocarbons, e.g., toluenes to carboxylic acids, under mild conditions. In the case of the less reactive cycloalkanes, NHS proved to be a more active catalyst than NHPI which is attributed to the higher reactivity of the intermediate nitroxyl radical, resulting from the replacement of a carbonyl group in NHPI by the more strongly electron-attracting sulfonyl group. Stable dialkylnitroxyl radicals, exemplified by TEMPO, catalyze oxidations of, e.g., alcohols, with single oxygen donors such as hypochlorite and organic peracids. The reactions involve the intermediate formation of the corresponding oxoammonium cation as the active oxidant. Alternatively, in conjunction with transition metals, notably ruthenium and copper, they catalyze aerobic oxidations of alcohols. These reactions involve metal-centered dehydrogenations and the role of the TEMPO is to facilitate regeneration of the catalyst (Ru and Cu) and oxidation of the alcohol (Cu) via hydrogen abstraction or one-electron oxidation processes. Detailed mechanistic investigations, including kinetic isotope effects, revealed that oxoammonium cations are not involved as intermediates in these reactions. In contrast, oxoammonium cations are involved in the aerobic oxidation of alcohols catalyzed by the copper-dependent oxidase, laccase, in combination with TEMPO. This different mechanistic pathway is attributed to the much higher redox potential of the copper(II) in the enzyme. Similarly, N-hydroxy compounds such as ...

Atmospheric‐Pressure, Liquid‐Phase, Selective Aerobic Oxidation of Alkanes Catalysed by Metal–Organic Frameworks

“…[8] In previous works, it has been reported that N-hydroxyphthalimide (NHPI), in combination with transition metal acetates, can promote the oxidation of cycloalkanes and alkylbenzenes with oxygen under homogeneous conditions by using acetic acid as the solvent. [9][10][11] However, the selectivity for the oxidation of industrially relevant cyclohexane by using NHPI was low due to the formation of significant amounts of dicarboxylic acids. A heterogeneous version of this system has been reported by using silica or zeolites as NHPI supports, which avoids the need for corrosive acetic acid.…”

Highly efficient and organic nitrogen‐containing cation‐promoted aerobic oxidation of alkylaromatics in the presence of N‐hydroxyphthalimide

“…17,18 In such processes, oxidation was achieved through the radical route and the active catalytic species of phthalimide N-oxyl radical (PINO) originated from NHPI under an oxygen atmosphere. 19,20 A catalyst system including NHPI and acetaldehyde showed promising catalytic performance in the oxidation of organic substrates in the absence of any metal.…”

An Oxygen‐Deficient Perovskite as Selective Catalyst in the Oxidation of Alkyl Benzenes

“…In contrast, the presence of a high number of oxygen vacancies could favor the activation of the NHPI to form the phthalimide N-oxyl radical (PINO), promoting the absorption of the hydrogen atom from the hydrocarbon to form an alkyl radical, which reacts with O 2 molecules to afford oxygenated compounds. [6][7][8][9][10][11] The hypostoichiometric perovskite was also very efficient in the aerobic oxidation of other alkyl aromatics (toluene or ethylbenzene; Table 2). In both cases, the conversion of alkyl aromatics was very high (> 99.5 %).…”

“…This reaction was carried out using various catalytic systems-(La,Sr) 0.5 (Mn,Co) 0.5 O 3Àd /NHPI, (La,Sr) 0.5 (Mn,Co) 0.5 O 3 / NHPI-and, for comparative purposes to benchmark the present state of the art, we employed Co(OAc) 2 /Mn(OAc) 2 / NHPI, which is the best catalytic system described in literature for soft reaction conditions. [6][7][8] The p-xylene conversion was 100 % for all the systems (Table 1). However, the product distribution is highly affected by the catalyst used.…”