Ketones dioxiranes

As oxiranes can be generated in situ from Oxone (potassium peroxomono-sulfate) and a ketone, dioxiranes are attractive oxidants for epoxidation reactions that may be rapid and may require only a simple workup. 

In the metal-free epoxidation of enones and enoates, practically useful yields and enantioselectivity have been achieved by using catalysts based on chiral electrophilic ketones, peptides, and chiral phase-transfer agents. (E)-configured acyclic enones are comparatively easy substrates that can be converted to enantiomeri-cally highly enriched epoxides by all three methods. Currently, chiral ketones/ dioxiranes constitute the only catalyst system that enables asymmetric and metal-free epoxidation of (E)-enoates. There seems to be no metal-free method for efficient asymmetric epoxidation of achiral (Z)-enones. Exocyclic (E)-enones have been epoxidized with excellent ee using either phase-transfer catalysis or polyamino acids. In contrast, generation of enantiopure epoxides from normal endocyclic... 

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. 

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. 

In the late 1970s, evidence showed that diaLkyl dioxiranes were generated in ketone—caroate, 2KHSO KHSO K SO, systems (106) and the mechanism of the reaction was determined (88,90) ... 

Cyclic 1,2-diamines are cleaved to diketones with dimethyl dioxirane. a-Diketones and a-hydroxy ketones are also cleaved by alkaline H202. HIO4 has... 

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. 

A number of chiral ketones have been developed that are capable of enantiose-lective epoxidation via dioxirane intermediates.104 Scheme 12.13 shows the structures of some chiral ketones that have been used as catalysts for enantioselective epoxidation. The BINAP-derived ketone shown in Entry 1, as well as its halogenated derivatives, have shown good enantioselectivity toward di- and trisubstituted alkenes. 

These ketones can also be used in kinetic resolutions.107 The carbohydrate-derived ketones have been used in conjunction with acetonitrile and H202. The reactions are believed to proceed through dioxiranes generated by a catalytic cycle involving a peroxyimidic acid.108... 

The epoxidation of nonfunctionalized alkenes may also be effected by chiral dioxiranes. These species, formed in situ using the appropriate ketone and potassium caroate (Oxone), can be formed from C-2 symmetric chiral ketones (29)[93], functionalized carbohydrates (30)[94] or alkaloid derivatives (31)[95]. One example from the laboratories of Shi and co-workers is given in Scheme 19. 

Among many other methods for epoxidation of disubstituted E-alkenes, chiral dioxiranes generated in situ from potassium peroxomonosulfate and chiral ketones have appeared to be one of the most efficient. Recently, Wang et /. 2J reported a highly enantioselective epoxidation for disubstituted E-alkenes and trisubstituted alkenes using a d- or L-fructose derived ketone as catalyst and oxone as oxidant (Figure 6.3). 

Epoxidation of alkenes can be effected by potassium persulphate. When the oxidation is conducted in the presence of chiral trifluoroketones, chiral oxiranes (ee 12-22%) are produced [14]. The chirality appears to be achieved via the initial reaction of the persulphate with the ketone to generate chiral dioxiranes, which then interact with the alkenes. 

Tetra-n-butylammonium hydrogen sulphate facilitates the enantiomeric epoxida-tion of alkenes by persulphates in the presence of chiral ketones (10.6.8). The reaction proceeds via the initial formation of chiral dioxiranes [23]. 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

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. 

Shi and coworkers developed a method using silyl enol ethers and in situ generated chiral dioxirane derivatives. Lopp and coworkers could develop an asymmetric dihydroxy lation method for racemic 2-hydroxymethyl ketones 202a-c, using TBHP as oxygen source in combination with the Sharpless catalytic system Ti(OPr-i)4/DET, yielding... 

Various ketones can be converted into the corresponding three-membered cyclic peroxides, i.e. dioxiranes by treatment with buffered aqueous solutions of Oxone (equation 44). 

Dioxirane chemistry is well documented . Extensive kinetic, stereochemical and 0-labeling data suggested that dimethyldioxirane is the oxygen-atom transfer reagent in the Oxone-acetone system . Murray and Jeyaraman have shown that dialkyl dioxiranes can be isolated by low-temperature distillation from the reaction mixture of oxone and ketone . 

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. 

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