Preparation of dimethyldioxirane

As a reagent, it is commonly found in the preparation of dimethyldioxirane (DDO). itself a useful oxidizing agent. 

The preparation of 2,3,5-trisubstituted 4,5-dihydrofurans 81 with complete regio-control can be realized by an one-pot transformation involving epoxidation of 2-alkenyl-1,3-dicarbonyls by in situ generated dimethyldioxirane, and is followed by a S-exo-ieX intramolecular nucleophilic cyclization under the same basic condition <00TL10127>. 

CgoO (1) can also be prepared by allowing toluene solutions of CgQ to react with dimethyldioxirane (Scheme 8.3) [28], The so-obtained product is identical to that prepared by photochemical epoxidation [15], Upon treatment of CgQ with dimethyldioxirane, a second product is formed simultaneously (Scheme 8.3), which was identified to be the 1,3-dioxolane 6. Upon heating 6 in toluene for 24 h at 110 °C, no decomposition could be observed by HPLC, implying that 1 and 6 are formed by different pathways. Replacement of dimethyldioxirane with the more reactive methyl(trifluoromethyl)dioxirane allows much milder reaction conditions [29]. At 0 °C and a reaction time of only some minutes this reaction renders a CgQ conversion rate of more than 90% and higher yields for CgoO as well as for the higher oxides. 

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. 

The preparation of the allene bis-epoxide 1 started with isovaleraldehyde 9. Addition of the protected propargyl alcohol 10 under the Carreira conditions led to 11 in > 95% . Mesylation followed by displacement with methyl cuprate provided the allene without loss of enantiomeric excess. Oxidation of the allene 12 with dimethyldioxirane could have led to any of the four diastereomers of the spiro bis epoxide. In the event, only two diastereomers were observed, as a 3 1 mixture. That 1 was the major diastereomer followed from its conversion to 3. The configuration of the minor diastereromer was not noted. Exposure of 1 to nucleophilic azide then gave the easily-purified 2. 

Apart from some aliphatic iodides, which have been oxidized directly to iodosyl derivatives with ozon or dimethyldioxirane [3], iodoarenes give directly iodylarenes with strong oxidants. From a synthetic point of view, potassium bro-mate in sulfuric acid has been used for the preparation of several members. The parent PhI02 can also be obtained by overoxidation of iodobenzene with peracetic acid, followed by hydrolysis as detailed in Organic Syntheses [36]. Another good method is oxidation of Arl by hypochlorite, at room temperature under phase transfer catalysis (Scheme 7) [37]. 

A series of allenic carboxylic acids has been converted to funtionalized P-lactones 47 by oxidation-cyclization promoted by pre-prepared solutions of dimethyldioxirane <02T7027>. This transformation is rationalized by the involvement of unisolated spirodioxide intermediates, which give lactones with appropriately situated cx-hydroxyketone moieties. 

Dioxirane (RR C02) compounds are relatively new in the arsenal of the synthetic chemist, however since the isolation of dimethyldioxirane by Murray and Jeyaraman in 1985,146 it has become a very important oxidant for preparative oxygen transfer chemistry.147 The dioxiranes are ideal oxidants in that they are efficient in their oxygen atom transfer, exhibit high chemio- and regio-selectivities, act catalytically, are mild towards the substrate and oxidized product, and perform under strictly neutral conditions. The compounds are prepared from peroxymonosulfate and ketones under neutral to mildly alkaline conditions (Figure 2.46). 

The dioxiranes can be used via either an in situ70 or an ex situ method.71 If the in situ method can be tolerated then better yields are afforded based on the primary oxidant employed, i.e. the peroxymonosulfate, whereas isolation of the dioxirane only yields about 5-10% based on the peroxymonosulfate. The in situ method is carried out in a two-phase manner, employing a solvent such as dichloromethane or toluene. The epoxidation ability of the dioxiranes is excellent, and the conditions relatively mild. The majority of epoxidations are carried out at ambient temperatures and pressures. Figure 3.18 summarizes the various epoxides which can be prepared in the presence of dimethyldioxirane (DMD). 

Determination of dimethyldioxirane concentration by the GLC method is as follows A standard solution of thioanisole (phenyl methyl sulfide) is prepared. The solution is usually 0.2 M in acetone, but other concentrations may be used. It is important to keep the sulfide in excess so that oxidation by the dioxirane will produce largely or exclusively the sulfoxide and not the sulfone. 

Reactions which formally involve the oxidation of azides have been reviewed by Boyer. Other oxidations with useful synthetic applications include two which start from nitrogen ylides. Sulfimides (50) derived from electron-deficient aromatic and heterocyclic amines are oxidized to the corresponding nitroso compounds by MCPBA. > This is a very useful method of preparation of some otherwise inaccessible nitroso compounds such as 2-nitrosopyridine and 1-nitrosoisoquinoline. They can be further oxidized, for example by ozone, to the nitro compounds. Phosphimides (51) are oxidized directly by ozone to the nitro compounds, although the nitroso compounds are intermediates. Isocyanates can also be oxidized to the corresponding nitro compounds, by dimethyldioxirane (1). ... 

Dimethyldioxirane (DMDO) is a mild reagent for epoxidation under neutral conditions of electron-rich as well as of electron-deficient alkenes.Moreover, dimethyldioxirane is often the oxidant of choice for the preparation of labile epoxides. The reagent is prepared by oxidation of acetone with potassium caroate KHSO5 (Oxone) and is stable in acetone solution at —20 °C for several days. ... 

To a stirred solution of methyl 2-cyclopropylidene-2-(phenylsulfanyl)acetate (29 25 mg, 0.11 mmol) " in anhyd acetone (1 mL), kept under argon at 0°C, was added within 1 min a 0.029 M soln of dimethyldioxirane in acetone (9 mL, 0.29 mmol), prepared according to the literature procedure." The mixture was stirred at 0 "C for 10 min and at rt for an additional 10 min. Evaporation of the acetone at rt on a rotatory evaporator under reduced pressure left a light yellow oil, which solidified upon standing in a refrigerator. According to its spectra ( H NMR, "C NMR, MS) it was pure 30 yield 26.7 mg (99%). 

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