Dioxiranes alkane oxidation

A new approach to the oxyfunctionalization of alkanes with isolated dioxiranes has been reviewed. Dioxiranes achieve oxidation of alkanes with high selectivity for both... 

In general, peroxomonosulfates have fewer uses in organic chemistry than peroxodisulfates. However, the triple salt is used for oxidizing ketones (qv) to dioxiranes (7) (71,72), which in turn are useful oxidants in organic chemistry. Acetone in water is oxidized by triple salt to dimethyldioxirane, which in turn oxidizes alkenes to epoxides, polycycHc aromatic hydrocarbons to oxides and diones, amines to nitro compounds, sulfides to sulfoxides, phosphines to phosphine oxides, and alkanes to alcohols or carbonyl compounds. 

This was also accomplished with BaRu(0)2(OH)3. The same type of conversion, with lower yields (20-30%), has been achieved with the Gif system There are several variations. One consists of pyridine-acetic acid, with H2O2 as oxidizing agent and tris(picolinato)iron(III) as catalyst. Other Gif systems use O2 as oxidizing agent and zinc as a reductant. The selectivity of the Gif systems toward alkyl carbons is CH2 > CH > CH3, which is unusual, and shows that a simple free-radical mechanism (see p. 899) is not involved. ° Another reagent that can oxidize the CH2 of an alkane is methyl(trifluoromethyl)dioxirane, but this produces CH—OH more often than C=0 (see 14-4). ... 

In addition to metal catalyzed oxygenation of nonactivated alkane C-H bonds, oxofunctionalization of C-H bonds can also occur in water by using dioxiranes.20 Alkylketones and alkylketoesters could be regioselectively oxidized at the 5-position of the aliphatic chain by dioxiranes generated in situ by oxone in a mixture of H20/MeCN... 

In regard to the stereoselectivity of the insertion process, Murray and coworkers have shown that the CH oxidation of substituted cyclohexanes by dioxiranes is, like the already discussed epoxidation, highly stereo-controUed . A specific case is c -decalin, which gives only the cis alcohol, as exemplarily displayed in equation 27. A similar stereoselective retention of configuration was also obtained for frawi-decalin and cis- and frawi-dimethylcyclohexanes"°. In fact, complete retention of configuration was demonstrated in the CH oxidation of chiral alkanes ". For example, the optically active (f )-2-phenylbutane was converted by either DMD or TFD" to (5 )-2-phenylbutan-2-ol (equation 28) without any loss of the enantiomeric purity (ep) in the product. 

When the C—H bond to be oxidized is proximate to a functional group, as we have stated already, its reactivity depends on the type of functional group. In the case of the hydroxy group, especially in secondary alcohols, these are more prone to dioxirane oxidation than their alkane precursors and, consequently, usually carbonyl products are obtained as the final product. Primary alcohols are less reactive, but may still be converted slowly to the corresponding aldehydes or carboxylic acids (due to the facile further oxidation of aldehydes)The functional-group transformation of the alcohols to ethers or acetals reduces the oxidative reactivity " but these C—H bonds are still more reactive than unfunctionalized ones. Thus, dioxirane oxidation of benzyl ether or acetal may... 

The oxidation of organic substances by cyclic peroxides has been intensively studied over the last decades , from both the synthetic and mechanistic points of view. The earliest mechanistic studies have been carried out with cyclic peroxides such as phthaloyl peroxide , and more recently with a-methylene S-peroxy lactones and 1,2-dioxetanes . During the last 20 years, the dioxiranes (remarkable three-membered-ring cyclic peroxides) have acquired invaluable importance as powerful and mild oxidants, especially the epoxidation of electron-rich as well as electron-poor alkenes, heteroatom oxidation and CH insertions into alkanes (cf. the chapter by Adam and Zhao in this volume). The broad scope and general applicability of dioxiranes has rendered them as indispensable oxidizing agents in synthetic chemistry this is amply manifested by their intensive use, most prominently in the oxyfunctionalization of olefinic substrates. 

Two new reactive, very powerful organic peroxides, dimethyldioxirane and methyl(trifluoromethyl)dioxirane (4), have been introduced.81-83 The latter is more reactive and can be used more conveniently.84 85 Acyclic alkanes give a mixture of isomeric ketones on oxidation with methyl(trifluoromethyl)dioxirane,84,85 while cyclohexanone is the sole product in the oxidation of cyclohexane (99% selectivity at 98% conversion).85 With the exception of norbomane, which undergoes oxidation at the secondary C-2 position, highly selective tertiary hydroxylations can be carried out with regioselectivities in the same order of magnitude as in oxidations by peracids.85-87 A similar mild and selective tertiary hydroxylation by perfluorodialkyloxaziridines was also reported.88 Oxidation with dioxiranes is highly stereoselective 85... 

Oxidation of alkanes to alcohols anil or ketones.1 This dioxirane oxidizes hydrocarbons in CH2Cl2/l,l,l-trifluoro-2-propanone (TFP) at -22 to 0° to alcohols or further oxidation products in high yield. Tertiary C-H bonds are attacked more rapidly than secondary ones, and primary C-H bonds are scarcely affected. The oxidation apparently involves insertion of O-atom. Oxidations can be stereospecific, as in the case of cis- and trans- 1,2-dimethyIcyclohexane. 

DMD is suitable for the oxidation of most substrates with substances that are resistant to oxidation, however, the more reactive but also more expensive methyl (trifluoromethyl)dioxirane (TFD) is necessary. The oxidation is stereoselective for both dioxiranes and proceeds with complete retention of configuration at the oxidized carbon atom (Scheme 1) [20-22]. The reactivity follows the usual order of electrophilic oxidation-primary < secondary < tertiary < benzylic < allylic C-H bonds. Except for tertiary C-H bonds, which produce the oxidatively inert tertiary alcohols, further oxidation of the primary product (an alcohol) to a ketone or aldehyde (the latter is readily further oxidized to the corresponding acid) is possible, because the a-hydrogen of the alcohol is usually more reactive than that of the unactivated alkane, especially for allylic C-H bonds. 

Oxidation of Unactivated Alkanes by Dioxiranes 507 Waldemar Adam and Cong-Gui Zhao... 

Dioxiranes, generated by the oxidation of ketones with KHSOs, insert an oxygen atom into alkane C—H bonds with retention of configuration by an oxenoid mechanism related to that found for peracids. Tertiary C—H bonds are hydroxylated and react faster than secondary CH2 groups, which are completely oxidized to the ketone. Conversions of up to 50% have been observed." CF3(Me)C02 is a more recently developed reagent of the same type. These easily prepared reagents have considerable promise for organic synthesis. 

Simple alkanes can be converted to esters with dialkyloxrranes. Cyclic alkanes are oxidized to alcohols with dimethyl dioxirane. " Cyclohexane was converted to cyclohexyl trifluoroacetate with di(trifluoromethyl) dioxrrane and trifluoroacetic anhydride and also with RuCl3/MeC03H/CF3C02H. Dimethyl dioxrrane converts alkanes to alcohols in some cases. Adamantane is converted to adamantyl alcohol with DDQ (p. 1710) and triilic acid. The mechanism of oxygen insertion into alkanes has been examined. ... 

The general features of reactivity and selectivity of this novel oxidant are displayed in Table 3. It is significant that the fluoro derivative, i.e. methyl-(trifluormethyl)dioxirane [6], is at least 1000-fold more reactive than dimethyldioxirane. As a consequence, the fluorinated dioxirane oxidizes alkanes to the corresponding alcohols and/or ketones within minutes even at subambient temperatures [7]. 

The unusual reactivity of dioxiranes is impressively exhibited in their ability to insert into C — H bonds (Scheme 7) [28]. Thus, tertiary alkanes are oxidized to their respective alcohols [29]. In the example shown, the insertion took place with complete retention of configuration at the chirality center. 1,3-Dicarbonyl derivatives [30] are hydroxylated with high efficiency, but more than likely the intermediary enol is being oxyfunctionalized. Secondary alcohols are transformed into ketones, a specific example is the oxidation of the epoxy alcohol in the rosette [31], In an attempt to epoxidize the hydroxy acrylic ester [22], the epoxy 1,3-dicarbonyl product was obtained, although in low yield in accord with its rather reluctant nature towards oxidation. 

There are many reviews that cover various aspects of oxidation. These include ones on alkane activation,166 catalytic selective oxidation,167 metal complexes of dioxygen,168 metal-catalyzed oxidation,169 biomimetic oxidations,170 oxidation with peroxides,171 catalytic oxidations with peroxides,172 catalytic oxidations with oxygen,173 oxidations with dioxiranes,174 and oxidation of pollutants.175... 

A theoretical study on the oxidation of methane, propane and isobutane with dioxirane, dimethyldioxirane, difluorodioxirane and methyl(trifluoromethyl)di-oxirane has provided a rational for the formation of radical intermediales when dioxygen is rigorously excluded and supported the generally accepted, highly exothermic, concerted oxygen insertion mechanism for the oxidation under typical preparative conditions. The activation barriers for the oxidation of methane (44.2), propane (30.3) and isohutane (22.4 kcal mol" ) with dimethyldioxirane have been evaluated [48e]. Perfluorodialkyloxaziridines are also mild and selective reagents for the hydroxylation of alkanes [49] ... 

Dioxiranes. These organic peroxygen compounds are relative newcomers to synthetic chemistry, but in the last ten years it has been shown that they are among the most powerful and versatile non-metal oxidants available to the organic chemist, with the ability to oxidise amines to nitro-compounds, to epoxidise very unreactive double bonds, and to hydroxy late alkanes and aromatic side-chains [26]. 

Alkenes, Allies, Arenes, and Alkanes. One of the most common apphcations of Oxone in organic synthesis is the in situ formation of dioxiranes fromketones (eq 1). Dioxrrane chemistry has grown significantly in recent years, particularly in the area of enantioselective epoxidation, and a wide variety of chiral ketones have been designed for this purpose. Notably, ketones (5 and 6) derived from fructose and glucose, respectively, have been shown to be effective catalysts for enantioselective epoxida-tions of a variety of trans-, trisubstituted, cis-, and terminal olefins with Oxone as primary oxidant (eqs 38 and 39). ... 

The oxidation of organic compounds by dioxiranes has attracted considerable interest in recent years. Bravo et al. have reported that the oxidation of a variety of organic compounds (alkanes, alcohols, ethers, aldehydes, and alkenes) by dimethyl-dioxirane may be explained via a radical mechanism. The proposed molecule-induced homolysis of dimethyldioxirane is supported by radical trapping with CBrCls or protonated quinolines. The presence of oxygen has also been shown to have a significant effect on these reactions and supports a radical mechanism. The... 

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