Peroxy acids ethers

Triethyl- and triphenylphosphine have been used for deoxygenation not only of hydroperoxides to alcohols but also of dialkyl peroxides to ethers, of diacyl peroxides to acid anhydrides, of peroxy acids and their esters to acids or esters, respectively, and of endoperoxides to oxides [290] in good to excellent yields. The deoxygenation of ascaridole to l-methyl-4-isopropyl-l,4-oxido-2-cyclohexene [290] was later challenged the product is claimed to be p-cymene instead [668]). 

Pathway G Synthesis of 2-(l-hydroxyalkyl)benzofuran derivatives from o-alkenylphenols. o-Allylphenols and their benzyl ethers (168), treated with a peroxy acid, give epoxides which, according to conditions, lead... 

A peroxy acid mediated oxidative rearrangement of 2-alkoxy-3,4-dihydro-2//- pyrans affords 5-alkoxytetrahydrofuran-2-carbaldehydes (79JCS(Pi)847>. This reaction pathway was used in developing a method for the synthesis of optically active monoalkylfurans. (S)-2-Ethoxy-5-s-butyl-3,4-dihydro-2//-pyran (319), obtained through a cycloaddition reaction of (S)-2-s-butylacrolein to ethyl vinyl ether, was converted to (S)-2-s-butyl-5-ethoxytetrahydrofuran-2-carbaldehyde (320) (Scheme 85). 

The synthesis of epoxy ethers by peroxy acid treatment of suitable vinylic ethers, on the other hand, is complicated by the acid sensitivity of epoxy ethers. For example, Bergmann and Mk>keley1Ss claimed in 1921 to have prepared 1 -ethoxy-1 (2 -epoxyethane by the oxidation of ethyl vinyl ether with perbenzoic aoid, bat B years later modified their structure to a dioxone type of dimer.186 In 1 B0 Mous-seron and co-wcrkere1168-1184 reported the preparation of an epoxy ether from 1 -ethoxy-1 -eydohexene, but 4 years later Stevens and Taznma164 showed the compound obtained in this oxidation, not to have the structure initially assigned to it. 

Epoxides (oxiranes) are three-membered cyclic ethers. The simplest and commercially most important example is ethylene oxide, manufactured from ethylene, air, and a silver catalyst. In the laboratory, epoxides are most commonly prepared from alkenes and organic peroxy acids. 

Enol ethers, and in particular silylated ends (see Volume 2, Chapter 2.3), react with peroxy acid reagents to give initially a silyloxy qpoxide, which rearranges with silyl migration to yield an a-silyloxy ketone, " as in Scheme 3. The net result is that a ketone is converted to a protected a-hydroxy ketone, and the stereochemistry b determined by the least hindered approach of the peroxy acid to the enol. 

The Kharasch-Sosnovsky reaction may be carried out in the presence of caiboxylic acids to introduce the acyloxy moiety of the acid used, and may also be conducted photochemically at room temperature using UV irradiation. Peroxy acids, diacyl peroxides, and peroxyphosphates and peroxyphospho-nates are alternative oxidants. r-Butyl hy operoxide may also be used in place of peroxy esters with broadly similar results, although formations of mixed peroxides and r-butyl ethers can then compete with allyl ester production. 

Another clilTerence between sulfides and ethers is that sulfides are easily oxidized. Treatment of a sulfide with hydrogen peroxide, H2O2, at room temperature yields the corresponding sulfoxide (R2SO), and further oxidation of the sulfoxide with a peroxy acid ydelds a sulfone (R2SO2). 

Peroxy acids. Konen and Silbert have developed a mild, general synthesis of peroxy acids entailing first acylation of silver diethyl phosphate in ether solution followed by perhydrolysis of the mixed anhydride with hydrogen peroxide (98%... 

In addition to the ozonolysis of alkenes and a few aromatic compounds [93, 104], ozone oxidizes other groups. Thus saturated hydrocarbons containing tertiary hydrogen atoms are converted into tertiary alcohols [105, 106], and some alkenes are transformed into epoxides [107] or a,p-unsat-urated ketones [108], Benzene rings are oxidized to carboxylic groups [109, ethers [110] and aldehyde acetals [111] to esters aldehydes to peroxy acids [772] sulfides to sulfoxides and sulfones [775] phosphines and phosphites to phosphine oxides and phosphates, respectively [775] and organomer-cury compounds to ketones or carboxylic acids [114]. 

Vinyl ethers and peroxy acids give primarily epoxides, which can be isolated [297] or which can react further with the reaction medium [314] (equations 329 and 330). 

When allowed to stand in ether or chloroform solution, the peroxy acid and the unsatiirated compound—which need not be a simple alkene—react to yield benzoic acid and the epoxide. For example ... 

On the other hand, no epoxide has been reported to be immune to reaction with BF3, although an interesting example of inertness was noted by Crandall and Machleder. Allene epoxides are usually too sensitive to acids to be isolable from peroxy acid epoxidations, but the bulky r-butyl groups on (70 equation 30) make it exceptionally unreactive. Several hours of reflux with BF3 in ether were required to effect the conversion to (71). 

In this reaction the C=C double bond acts as a nucleophile, and in most acyclic or monocyclic molecules oxygen is added with equal facility to the top or bottom face of the alkene. Oxiranes are the most reactive ethers, and are readily susceptible to nucleophilic attack, which results in ring opening. This is in contrast to diethyl ether (ethoxyethane), which is inert even in the presence of, for example, LiAlH4. Likewise, 1,2-dimethylcyclohexene (27) reacts with peroxy acids to give cis-1,2-dimethylcyclohexene oxide (28). 

Drugs that are susceptible to oxidation of carbon-hydrogen bonds include ethers (which oxidise to form highly explosive peroxides), aliphatic amines (which oxidise at the a hydrogen atom) and aldehydes (which are easily oxidised to carboxylic acids and peroxy acids). Examples of these reactions are shown in Figure 8.6. 

In ketone-directed peroxy acid epoxidations of cyclic alkenes the actual epoxidizing agent has been shown by 180-labeling not to involve a dioxirane <94TL6155>. Instead, an a-hydroxy-benzoylperoxide or a carbonyl oxide is believed to be responsible for observed stereoselectivities in the intramolecular epoxidations. The extent of syn-selectivity is greater for ketones than with esters the syn/anti ratios increase when ether is used as solvent rather than CH2C12, the reverse situation for hydroxyl-directed epoxidations. Fused-ring oxiranes can also be prepared from acyclic precursors. Four different approaches are discussed below. 

Dienolic ethers (379), in contrast with the acetates, are cleaved by peroxy-acid at the 3,4-unsaturated link under anhydrous conditions, giving carbo-methoxy-aldehydes (380). The reaction is probably mechanistically similar to the oxidative cleavage of dihydropyrans e.g. 381 — 382), although the... 

Furost-20(22)-enes (384) react with peroxy-acid with introduction of a hydroxy-group at the 20a-position, and ring closure to give the 20a-hydroxy-spirostan (385). The isolation of up to 25% of the 20,23-diol (386) is attributed to contamination of the furost-20(22)-ene with the 22(23)-unsaturated isomer. Almost all 3,5-dienolic esters and ethers react with electrophiles at C-6, apart from rare instances of reaction at C-4 or C-2 (see above). Reaction between the dienolic ethers (387) and tetranitromethane in ether has now been shown to afford the 2 -nitro-derivatives (388). No mechanistic details are available, but it is tempting to suggest the involvement of free-radicals derived from the reagent. 

The oxidation of unsaturated compounds by organic peroxy acids in anhydrous solvents such as chloroform, ether, dioxan, benzene, or acetone proceeds with formation of 1,2-epoxides according to the equation ... 

---