Epoxidation peracid

The alkene substrate is first dispersed in the reactor with the carboxylic acid in the presence of a solvent if necessary. Addition of hydrogen peroxide forms the peracid which facilitates epoxidation, and re-generates the carboxylic acid for further reaction. In consequence only low levels of carboxylic acid are required (0.2-0.3 mol per mol of double bond). This also has the advantage of reducing epoxide loss to acid-catalysed ring-opening. The application of two phases with or without the presence of solvent also improves the efficiency of the epoxidation. Peracids most suited to epoxidation in situ are performic and peracetic acid. 

Perfluoroepoxides have also been prepared by anodic oxidation of fluoroalkenes (39), the low temperature oxidation of fluoroalkenes with potassium permanganate (40), by addition of difluorocarbene to perfluoroacetyl fluoride (41) or hexafluoroacetone (42), epoxidation of fluoroalkenes with oxygen difluoride (43) or peracids (44), the photolysis of substituted l,3-dioxolan-4-ones (45), and the thermal rearrangement of perfluorodioxoles (46). 

Garyophyllene. (-)-CaryophyUene can be isolated from Indian turpentine and has been used to prepare a number of woody aroma products. The epoxides are produced by reaction with peracids. Acetylation of caryophyUene also gives a usehil methyl ketone (180) (Fig. 8). Acid-catalyzed rearrangement of caryophyUene in the presence of acetic acid gives a mixture of esters, which are related to caryolan-l-ol and clovan-2-ol (181). 

The double bonds of avermectins react with y -chloroperbenzoic acid to give 3,4-, 8,9-, and 14,15-epoxides. The 8,9-epoxide is the primary product and can be isolated in good yield (45). The 8,9-epoxide was opened by aqueous acids to the 8,9-diol (46). The 3,4-diol can be obtained readily and regiospecificaHy by osmium tetroxide oxidation. Neither peracids nor OsO will attack the 22,23-double bond. 

Butadiene can also be readily epoxidized with peracids to the monoepoxide or the diepoxide (109,110). These have been proposed as important intermediates in the metaboHc cycle of butadiene in the human body (111). 

Transition metal-catalyzed epoxidations, by peracids or peroxides, are complex and diverse in their reaction mechanisms (Section 5.05.4.2.2) (77MI50300). However, most advantageous conversions are possible using metal complexes. The use of t-butyl hydroperoxide with titanium tetraisopropoxide in the presence of tartrates gave asymmetric epoxides of 90-95% optical purity (80JA5974). 

Oxaziridines are generally formed by the action of a peracid on a combination of a carbonyl compound and an amine, either as a Schiff base (243) or a simple mixture. Yields are between 65 and 90%. Although oxygenation of Schiff bases is formally analogous to epoxidation of alkenes, the true mechanism is still under discussion. More favored than an epoxidation-type mechanism is formation of a condensation product (244), from which an acyloxy group is displaced with formation of an O—N bond. 

The high degree of stereoselectivity associated with most syntheses and reactions of oxiranes accounts for the enormous utility of these systems in steroid syntheses. Individual selectivity at various positions in the steroid nucleus necessitates the discussion of a collection of uniquely specific reactions used in the synthesis of steroidal epoxides. The most convenient and generally applicable methods involve the peracid, the alkaline hydrogen peroxide and the halohydrin reactions. Several additional but more limited techniques are also available. 

The most common method of epoxidation is the reaction of olefins with per-acids. For over twenty years, perbenzoic acid and monoperphthalic acid have been the most frequently used reagents. Recently, m-chloroperbenzoic acid has proved to be an equally efficient reagent which is commercially available (Aldrich Chemicals). The general electrophilic addition mechanism of the peracid-olefin reaction is currently believed to involve either an intra-molecularly bonded spiro species (1) or a 1,3-dipolar adduct of a carbonyl oxide, cf. (2). The electrophilic addition reaction is sensitive to steric effects. 

However, suitably located hydroxyl and acetoxyl functions can assist the cisoid approach of the peracid reagent. While 4jS-acetoxycholest-5-ene gives a 9 1 ratio of the a- and jS-epoxides, the 4a-acetoxy-5-ene yields the a-epoxide exclusively. The directive effect can be used to prepare and /9-oxiranes from A -steroids as illustrated by the epoxidation of (16) and (18). 

Many selective epoxidations are possible with polyunsaturated steroids. In general, oc, -unsaturated ketones are not attacked by peracid, although linear dienones react slowly at the y,5-double bond. Aw-Chloroperbenzoic acid is the reagent of choice for this reaction.When two isolated double bonds are present in the steroid nucleus, e.g. (27) and (30), the most highly substituted double bond reacts preferentially with the peracid. Selective epoxidation of the nuclear double bond of stigmasterol can likewise be achieved.However, one exception to this general rule has been reported [See (33) (34)]. ... 

Anomalous results in the peracid reaction are usually encountered when the resulting epoxides are particularly sensitive to acid. For this reason A - and A -steroid epoxides are difficult to isolate. The rearrangements... 

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

As electrophilic substitutes for peracids, the use of borate ester induced decomposition of alkyl hydroperoxides and molybdenum VI peroxy-complexes have been reported in the recent literature. Although these reagents have led to the epoxidation of olefins in greater than 90% yield there are no reports yet of their application to steroid olefins. 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

In analogy with the peracid attack on steroidal double bonds, the formation of the bromonium ion, e.g., (81a), occurs from the less hindered side (usually the a-side of the steroid nucleus) to give in the case of the olefin (81) the 9a-bromo-l l -ol (82). Base treatment of (82) provides the 9 5,1 l S-oxide (83). Similarly, reaction of 17/3-hydroxyestr-5(10)-en-3-one (9) with A -bromosuccinimide-perchloric acid followed by treatment with sodium hydroxide and sodium borohydride furnishes the 3, 17 5-dihydroxy-5a,l0a-oxirane. As mentioned previously, epoxidation of (9) with MPA gives the 5, 10 -oxirane. °... 

Although steroidal spiro oxiranes are difficult to obtain stereochemically pure by peracid epoxidations of exocyclic methylenes,the recently developed methylene transfer reagents, dimethylsulfonium methylide and di-methylsulfoxonium methylide in tetrahydrofuran, proved useful in the stereoselective transformation of steroid ketones to a- and -oxiranes, (87) and (88), respectively. ... 

Epoxidation with peracid, and mild alkaline hydrolysis proceeds to give the 17a-hydroxy-20-ketone in a high overall yield. ... 

The 20-acetylamino-17a,20-epoxide formed by reaction with peracid is also relatively stable to mild alkali, again permitting hydrolysis of a 3y5-acetoxy function. 

To overcome this, the A -acetyl group is reduced with lithium aluminum hydride. The resulting basic enamine then reacts extremely rapidly and selectively with peracid. The derived epoxide is hydrolyzed very easily with alkali during the workup. 

C-20 enol acetates react with peracids in the same manner as their C-17(20) counterparts, giving a 20,21-epoxide capable of cleavage to the 21-hydroxy-20-ketone ... 

When the OAc group was a hydroxyl, the epoxidation selectivity was not very good, presumably because of the known directing effect of hydroxyl groups in peracid epoxidations. 

The Prilezhaev reaction is a rarely used name for the epoxidation of an alkene 1 by reaction with a peracid 2 to yield an oxirane 3. The epoxidation of alkenes has been further developed into an enantioselective method, that is named after Sharpless. 

The hydroxy oxygen of a peracid has a higher electrophilicity as compared to a carboxylic acid. A peracid 2 can react with an alkene 1 by transfer of that particular oxygen atom to yield an oxirane (an epoxide) 3 and a carboxylic acid 4. The reaction is likely to proceed via a transition state as shown in 5 (butterfly mechanism), where the electrophilic oxygen adds to the carbon-carbon n-hond and the proton simultaneously migrates to the carbonyl oxygen of the acid ... 

The reactions of olefins with peracids to form epoxides allows for the selective oxidation of carbon-carbon double bonds in the presence of other functional groups which may be subject to oxidation (for example, hydroxyl groups). The epoxides that result are easily cleaved by strong acids to diols or half-esters of diols and are therefore useful intermediates in the synthesis of polyfunctional compounds. 

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