Reactivity dioxiranes

Other ketones besides acetone can be used for in situ generation of dioxi-ranes by reaction with peroxysulfate or another suitable peroxide. More electrophilic ketones give more reactive dioxiranes. 3-Methyl-3-trifluoromethyldioxirane is a more reactive analog of DMDO.99 This reagent, which is generated in situ from 1,1,1-trifluoroacetone, can oxidize less reactive compounds such as methyl cinnamate. 

AMI and PM3 calculations reveal that epoxidations by DMDO and TFDO involve peroxide-bond cr at a very early stage and that TFDO is the most reactive dioxirane as the CF3 group in it stabilizes this cr level. In accord with previous calculations a spiro transition state is predicted. Furthermore, allene is predicted to be less reactive than alkenes toward epoxidation by DMDO.192 DFT calculations on the oxidation of primary amines by dimethyldioxirane predict a late transition state with a barrier of 17.7 kcal mol-1 which is drastically lowered by hydrogen bonding to the O—O bond to just 1.3 kcal mol-1 in protic solvents.193... 

Denmark et al. reported a general protocol for the catalytic epoxidation of alkenes by in r// -generated reactive dioxiranes capable of epoxidizing a variety of alkenes under biphasic conditions <1995JOC1391>. The epoxide diastereoselectivity (Scheme 4) showed pronounced dependence on the solvent used since the ratio of diastereo-mers, as well as the distribution between epoxide and enone products, is dependent on the solvent <1995TL2437, 1999TL8023>. Selected examples are given in Table 2. 

Ketones other than acetone can be used for the formation of dioxiranes. Methyl(trilluoromethyl)dioxirane, formed from KHSO5 and the more electrophilic ketone trilluoroacetone, is a reactive dioxirane. This reagent can be used for the epoxidation of electron-poor a,p-unsaturated carbonyl compounds. Trifluoroace-tone can be used as a catalyst in combination with, for example, hydrogen peroxide... 

Halogen substitution is expected to increase the electrophilicity of the carbenes, and in particular lh with four fluorine substituents is expected to be highly electrophilic and of unusual reactivity. All the carbenes le-g could be matrix-isolated by irradiation of their corresponding quinone diazides 2 in argon at 8-10 K.24 68,62 Again, the thermal reaction in (Vdoped matrices results in the formation of quinone oxides 7, which show the expected photochemical rearrangement to the spiro dioxiranes 8 and finally lactones 9. 

The relative reactivity of a wide series of nucleophiles towards dioxirane, dimethyidioxirane, carbonyl oxide, and dimethylcarbonyl oxide has been examined at various levels of theory. The general trend in reactivity for oxidation by dioxirane was R2S R2SO, R3P > R3N in the gas phase, and R2S R2SO, R3N R3 (R = Me) in solution. A theoretical study of the first oxidation step of [3.2.1]-bridged bicyclic disulfides highlights a highly oriented reaction path was probably responsible for stereoselective attack on the exo face. ... 

A high catalyst loading (typically 20-30 mol%) is usually required for the epoxidation with ketone 26 because Baeyer-Vilhger oxidation presumably decomposes the catalyst during the epoxidation. The fused ketal moiety in ketone 26 was replaced by a more electron-withdrawing oxazohdinone (32) and acetates (33) with the anticipation that these replacements would decrease the amount of decomposition via Baeyer-Villiger oxidation (Fig. 8) [71, 72]. Only 5 mol% (1 mol% in some cases) of ketone 32 was needed to get comparable reactivity and enantioselectivity with 20-30 mol% of ketone 26 [71]. Since dioxiranes are electrophilic reagents, they show low reactivity toward electron-deficient olefins, such as a, 3-unsaturated esters. Ketone 33, readily available from ketone 26, was found to be an effective catalyst towards the epoxidation of a, 3-unsaturated esters [72]. 

Hexafluoroacetone and hydrogen peroxide in buffered aqueous solution epoxidize alkenes and allyhc alcohols.81 82 A/yV-Dialkylpiperidin-4-one salts are also good catalysts for epoxidation.83 84 The quaternary nitrogen enhances the reactivity of the ketone toward nucleophilic addition and also makes the dioxirane intermediate more reactive. 

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. 

These highly reactive 1,3-dipolar species readily isomerize and undergo 1,3-cycloaddition reactions in addition to their cyclization to the corresponding dioxirane. It is within this latter context that we describe the more recent theoretical studies on carbonyl oxides and their relationship to dioxiranes. As a result of the lability of carbonyl oxides much of the research on this class of compound has been of a theoretical nature ... 

A typical closed-shell transition structure for DMDO epoxidation is exemplified by the epoxidation of E- and Z-2-butene. Baumstark and Vasquez have reported experimental studies that demonstrate the greater reactivity of Z-alkenes in the DMDO epoxidation of E/Z-pairs of alkenes . As anticipated, approach of the dioxirane ring to the Z-double bond in the less hindered manner, away from the methyl groups of DMDO,... 

From this series of calculations it is noted that the gas-phase reactivity of TFDO is substantially greater than that of DMDO. This rate difference has been ascribed largely to the inductive effect of the CF3 group. Fluoro-substituted dioxiranes have also played a unique role in the chiral epoxidation of alkenes. Flouk and coworkers have identified a novel stereoelectronic effect that increases the rate of epoxidation when the fiuorine substituent is anti to the oxygen of the developing C=0 group in the TS for epoxidation. 

Part of the mystique surrounding the often assumed high reactivity of dioxiranes stems from the observation that dioxiranes such as methyl(trifluoromethyl)dioxirane (TFDO) are capable of oxidizing saturated hydrocarbons to their alcohols at relatively low temperatures in high yields and with impressive stereoselectivities (equation 8). 

Dioxiranes 18 have been suggested as the reactive intermediates in the oxidation in these reactions. 

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 dioxirane stmcture was postulated by Baeyer and ViUiger as a reactive intermediate in the Caroate oxidation of menthone. ... 

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