Dioxiranes epoxidation

Dioxiranes are remarkably versatile oxidizing agents which show encouraging potential for asymmetric synthesis, particularly asymmetric epoxidation. Dioxiranes can be generated in situ from Oxone (KHSO5) and ketones (Scheme 1). In principle, only a catalytic amount of ketone is required, so with a chiral ketone there exists the opportunity for catalytic asymmetric epoxidation." Since the first asymmetric epoxidation of olefins with a chiral dioxirane reported by Curci in 1984," this area has received intensive interest and significant progress has been made." - ... 

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. 

Development of chiral, nonracemic dioxiranes for the catalytic enantioselective epoxidation of alkenes 99SL847. 

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

Asymmetric epoxidation of terminal olefins has remained problematic, despite the general success of the novel dioxirane-based catalysts. The enantiomeric excesses in these reactions do not usually exceed 85% (see Section 9.1.1.1). As recrystallization of epoxides can be complicated, enantiopure terminal epoxides are difficult to obtain. 

The cyclohexyloxy(dimethyl)silyl unit in 8 serves as a hydroxy surrogate and is converted into an alcohol via the Tamao oxidation after the allylboration reaction. The allylsilane products of asymmetric allylboration reactions of the dimethylphenylsilyl reagent 7 are readily converted into optically active 2-butene-l, 4-diols via epoxidation with dimethyl dioxirane followed by acid-catalyzed Peterson elimination of the intermediate epoxysilane. Although several chiral (Z)-y-alkoxyallylboron reagents were described in Section 1.3.3.3.3.1.4., relatively few applications in double asymmetric reactions with chiral aldehydes have been reported. One notable example involves the matched double asymmetric reaction of the diisopinocampheyl [(Z)-methoxy-2-propenyl]boron reagent with a chiral x/ -dialkoxyaldehyde87. 

Many other reagents for converting alkenes to epoxides,including H2O2 and Oxone , VO(0-isopropyl)3 in liquid C02, ° polymer-supported cobalt (II) acetate and 02, ° and dimethyl dioxirane.This reagent is rather versatile, and converts methylene oxiranes to spiro-epoxides. ° ° One problem with dimethyloxirane is C—H insertion reactions rather than epoxidation. Magnesium monoperoxyphthalate is commercially available, and has been shown to be a good substitute for m-chloroperoxybenzoic acid in a number of reactions. 

Epoxidation by Dioxirane Derivatives. Another useful epoxidizing agent is dimethyldioxirane (DMDO),86 which is generated by in situ reaction of acetone and peroxymonosulfate in buffered aqueous solution. Distillation gives about aO.lM solution of DMDO in acetone.87... 

Various computational models agree that the reaction occurs by a concerted mechanism.91 Comparison between epoxidation by peroxy acids and dioxiranes suggests that they have similar transition structures. 

Scheme 12.12 gives some examples of epoxidations involving dioxiranes. Entry 1 indicates the ability of the reagent to expoxidize deactivated double bonds. Entry 2... 

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. 

This synthesis is shown in Scheme 13.59. Two enantiomerically pure starting materials were brought together by a Wittig reaction in Step C. The aldol addition in Step D was diastereoselective for the anti configuration, but gave a 1 1 mixture with the 6S, 1R-diastereomer. The stereoisomers were separated after Step E-2. The macrolactonization (Step E-4) was accomplished by a mixed anhydride (see Section 3.4.1). The final epoxidation was done using 3-methyl-3-trifluoromethyl dioxirane. 

Vinyl epoxides are highly useful synthetic intermediates. The epoxidation of dienes using Mn-salen type catalysts typically occurs at the civ-olefin. Epoxidations of dienes with sugar-derived dioxiranes have previously been reported to react at the trans-olefin of a diene. A new oxazolidinone-sugar dioxirane, 9, has been shown to epoxidize the civ-olefin of a diene <06AG(I)4475>. A variety of substitution on the diene is tolerated in the epoxidation, including aryl, alkyl and even an additional olefin. All of these substitutions provided moderate yields of the mono-epoxide with good enantioselectivity. 

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. 

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). 

An important finding is that all peroxo compounds with d° configuration of the TM center exhibit essentially the same epoxidation mechanism [51, 61, 67-72] which is also valid for organic peroxo compounds such as dioxiranes and peracids [73-79], The calculations revealed that direct nucleophilic attack of the olefin at an electrophilic peroxo oxygen center (via a TS of spiro structure) is preferred because of significantly lower activation barriers compared to the multi-step insertion mechanism [51, 61-67]. A recent computational study of epoxidation by Mo peroxo complexes showed that the metallacycle intermediate of the insertion mechanism leads to an aldehyde instead of an epoxide product [62],... 

The similarity of olefin epoxidation by TM peroxo and hydroperoxo complexes with epoxidation by dioxirane derivatives R2CO2 and percar-boxylic acids RCO(OOH) was confirmed by computational studies [73-79]. This similarity holds in particular for the spiro-type transition structure. 

Based on these calculations, one can conclude that TSs for epoxidation of alkenes and allylic alcohols with peroxy acids, dioxiranes, and Re-peroxo complexes share a spiro geometry in which the plane of the attacking peroxo... 

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. 

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