Ketones oxidation with dimethyldioxirane

Dioxiranes, three-membered-ring cyclic peroxides, are known as highly efficient and selective oxidants, capable of performing a variety of transformations for synthetic purposes. It is known that some reactions of these peroxides are accompanied by chemiluminescence due to the release of singlet oxygen. For instance, infra-red chemiluminescence (IR-CL) of O2 at A, 1270 nm is emitted in the reaction of tertiary amines and N-oxides with dimethyldioxirane (DMD) and methyl(trifluoromethyl)dioxirane (TFD), as well as during the anion-catalyzed breakdown of the dioxiranes. Furthermore, IR-CL emission is produced in the ketone-catalyzed decomposition of the monoperoxysulfate ion HSOs through the intermediary dioxirane. ... 

Enolization of racemic ketone 122 with the chiral lithium amide 123 produced a mixture of regioisomeric enol silanes 124 and 125 [78]. A treatment with PhSeCl and subsequent oxidation with dimethyldioxirane afforded the enones 126 and 127. This result shows a regiodivergent KR of racemic ketone 122. 

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... 

A mixture of epoxides 483 obtained on oxidation of 482 with dimethyldioxirane, when exposed to ferric chloride provided, as the kinetically controlled product, the a-aldehyde 484, which without purification was reduced to the a-alcohol 485. The exclusive formation of 484 is believed to occur via the benzyl cation 486, generated by Lewis-acid opening of the oxirane ring, suffering a stereospecific kinetic 1,2-hydride shift The amino alcohol 487 obtained after sequential removal of O-benzyl and N-tosyl groups from 485, on treatment with triphenylphosphine and iodine in the presence of imidazole furnished the tetracyclic base 488, which was oxidised to the ketone 489. Trapping of the kinetically generated enolate of 489 as the silylether, followed by palladium diacetate oxidation yielded the enone 490. The derived... 

The method is also successful for carboxyhc esters , and A,A-disubstituted amides, and can be made enantioselective by the use of a chiral oxaziridine. Dimethyldioxirane also oxidizes ketones (through their enolate forms) to a-hydroxy ketones. Titanium enolates can be oxidized with tert-butyl hydroperoxide or with dimethyl dioxirane and hydrolyzed with aqueous ammonium fluoride to give the a-hydroxy ketone. Ketones are converted to the a-oxamino derivative (0=C CH2- 0=C CHONHPh) with excellent enantioselectivity using... 

For the epoxidation of extremely unreactive alkenes and for the preparation of epoxides which are highly susceptible to nucleophilic attack, Dimethyldioxirane is the reagent of choice. Electron-deficient alkenes such as a, -unsaturated ketones are usually oxidized with Hydrogen Peroxide/base. 

The reaction of allenes with peracids and other oxygen transfer reagents such as dimethyldioxirane (DM DO) or hydrogen peroxide proceeds via allene oxide intermediates (Scheme 17.17). The allene oxide moiety is a versatile functionality. It encompasses the structural features of an epoxide, an olefin and an enol ether. These reactive intermediates may then isomerize to cyclopropanones, react with nucleophiles to give functionalized ketones or participate in a second epoxidation reaction to give spirodioxides, which can react further with a nucleophile to give hydroxy ketones. 

The synthetically most useful method for the preparation of dioxiranes is the reaction of appropriate ketones (acetone, trill uoroacetone, 2-butanone, cyclohexanone etc.) with Caroate, commercially available as the triple salt of potassium monoperoxysul-fate (KHSOs). The catalytic cycle of the dioxirane formation and oxidation is shown in Scheme 1 in general form. For acetone as the ketone, by simple distillation at a slightly reduced pressure ca 100 torr) at room temperature ca 20 °C), Jeyaraman and Murray successfully isolated dimethyldioxirane (DMD) as a pale yellow solution in acetone (maximally ca 0.1 M). This pivotal achievement in 1985 fomented the subsequent intensive research activity in dioxirane chemistry, mainly the synthetic applications but also the mechanistic and theoretical aspects. The more reactive (up to a thousandfold ) fluorinated dioxirane, methyl(trifluoromethyl)dioxirane (TFD), was later isolated in a similar manner by Curd, Mello and coworkers". For dioxirane derived from less volatile ketones, e.g. cyclohexanone, the salting-out technique has been developed by Murray and coworkers to obtain the corresponding dioxirane solution. 

Enantiopure A-protected a-aminoglyoxals are readily accessible by oxidation of a-diazo ketones, derived from amino acids using dimethyldioxirane, and their condensation with benzene-1,2-diamine in ethanol furnishes optically active quinoxalines in > 90% yield. 

The formal addition of an oxygen atom across the carbonyl group gives rise to dioxiranes (equation 33). In practice, this reaction is effected with Oxone, and dimethyldioxirane (30) and other dioxiranes have been generated in solutions of their parent ketones.Dioxirane (30) has been implicated in oxidations of alkenes, sulfides and iinines. The formal addition of nitrogen across a carbon-oxygen double bond to afford oxaziridines has been reviewed (equation 34).There are also many methods available for the indirect conversion of carbonyl compounds to aziridines > and thiiranes using multi-step conversions. 

Recently, dioxiranes, which are available in solution by the reaction of ketones with monoperoxy sulfate, were demonstrated to be selective and efficient oxidizing agents [10]. Such diluted solutions, e.g. of dimethyldioxirane which can be stored at -20 °C, can be used for the epoxidation of various olefins, too. If chiral ketones are employed for the generation of dioxirane solutions, an optical induction should be expected after the epoxidation of the olefins. 

Dimethyldioxirane is a relatively strong oxidant but can show good selectivity its reactivity is similar to that of a peracid but it has the advantage of producing a neutral byproduct (acetone). Methyl(trifluoromethyl)dioxirane is a more powerful oxidant which can insert oxygen into C-H bonds with retention of configuration, as shown below." Dioxiranes are obtained by reaction of ketones with OXONE NOTE Dioxiranes are explosive and are usually handled in dilute solution. 

This reaction was first reported by Rubottom and Brook et al. concurrently in 1974. It is the transformation of a ketone into the corresponding a-hydroxyketone by means of the epoxidation or dihydroxylation of a silyl enolate of the ketone with wi-chloroperbenzoic acid (m-CPBA) or dimethyldioxirane (DMDO). Therefore, this reaction is generally known as the Rubottom reaction or Rubottom oxidation. Under certain conditions, the Rubottom oxidation can establish a hydroxyl group enantioselectively, such as in the introduction of cw-hydroxyl group with respect to the isopropyl group in 8Q ,llj0-dimethyl-13)3-hydroxy-12/3-isopropyl-5/3,15-isopropylidenedioxy-14-keto-(A , A " )-tricycle. The silyl group can be cleaved by means of tetra-A-butylammonium fluoride (TBAF). ... 

Ketones and Other Oxygen Functions. Various ketones can be converted to the corresponding dioxiranes by treatment with buffered aqueous solutions of Oxone (eq 1). Of particular interest are dimethyldioxirane (R = R = Me) and methyl(trifluoro-methyl)dioxirane (R = Me, R = CF3) derived from acetone and l,l,l-trifluoro-2-propanone, respectively. The discovery of a method for the isolation of dilute solutions of these volatile dioxiranes in the parent ketone by codistillation from the reaction mixture has opened an exciting new area of oxidation chemistry. Solutions of dioxiranes derived from higher molecular weight ketones have also been prepared. ... 

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