Epoxidation chloroperbenzoic acid

The other main illogical electrophiles are epoxides, easily made from an olefin and a per-acid, the usual one being m-chloroperbenzoic acid (MCPBA) a commercial product. A more detailed explanation comes later, in fiiames 276-7. 

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. 

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. 

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)]. ... 

In a typical Knof procedure, 3jS-hydroxyandrost-5-en-17-one acetate is epoxidized with perbenzoic acid (or m-chloroperbenzoic acid ) to a mixture of 5a,6a- and 5)5,6)5-epoxides (75) in 99 % yield. Subsequent oxidation with aqueous chromium trioxide in methyl ethyl ketone affords the 5a-hydroxy-6-ketone (76) in 89% yield. Baeyer-Villiger oxidation of the hydroxy ketone (76) with perbenzoic acid (or w-chloroperbenzoic acid ) gives keto acid (77) in 96% yield as a complex with benzoic acid. The benzoic acid can be removed by sublimation or, more conveniently, by treating the complex with benzoyl chloride and pyridine to give the easily isolated )5-lactone (70) in 40% yield. As described in section III-A, pyrolysis of j5-lactone (70) affords A -B-norsteroid (71). Knof used this reaction sequence to prepare 3)5-hydroxy-B-norandrost-5-en-17-one acetate, B-noran-... 

Epoxidation of olefins with meta-chloroperbenzoic acid, (MCPBA) remains to this day among the most widely used methods for research-scale applications [16], Discovered by Nikolai Prilezahev in 1909 [17], it became popular only decades later, mostly through the works of Daniel Swern in the 1940s [18]. Despite its simplicity, and not unlike most epoxidation methods in use today, it suffers from undesired epoxide opening caused by the slight acidity of the reaction milieu. Although acid-catalyzed side reactions can sometimes be minimized by use of buffered systems... 

Dihydroxylation of 59a with osmium tetroxide in pyridine and epoxidation of 59a with m-chloroperbenzoic acid (mCPBA) both showed high syn preference of the addition (0 0 syn anti = 95 5 mCPBA synianti = 92 8). This preference is in sharp contrast to the anti preference of 60a (symanti = 12 88), observed under similar dihydroxylation conditions with osmium tetroxide in pyridine. 

Epoxidation of substituted spiro[cyclopentane-l,9 -fluorene]-2-enes 68 with a peroxidic reagent was studied [98], The spiro olefins react with m-chloroperbenzoic acid (mCPBA) in chloroform at 3 °C to give a mixture of the epoxides. In all cases (2-nitro (68b), 4-nitro (68c), 2-fluoro (68d) and 2-methoxyl (68e) groups), the iyn-epoxides, i.e., the syn addition of the peroxidic reagent with respect to the substituent, is favored. For example, for 6 nsyn anti = 63 31 for 68c syn anti = 65 35. Thus, a similar bias is observed in both the reduction of the carbonyl derivatives of 30 and the epoxidation of the derivatives of 68. 

The quantitative bulk conversion of unsaturated functional groups in PHAs to epoxides has been achieved by reaction with m-chloroperbenzoic acid as the chemical reagent [107]. No chain scission of the macromolecular chain was observed. Epoxy-modified PHAs are chemically even more reactive than unsaturated PHAs and therefore could be useful in further chemical reactions (e.g. grafting of therapeutic important substances) [108]. 

Epoxidation of J) with m-chloroperbenzoic acid afforded a mixture of the anti and syn diol epoxides (anti-and syn-BePDE). In our initial studies only the anti isomer was isolated (48). Subsequently, it was found by Yagi et al. (50) that both diastereomers are formed. In our experience, the relative ratio of isomers is dependent upon experimental conditions. This is another example of lack of stereospecificity of epoxidation of a diaxial dihydrodiol. 

Epoxidation of 10 with m-chloroperbenzoic acid yielded the chrysene anti-1,2-diol-3,4-epoxide, whereas similar reaction of 11 gave a mixture of the corresponding anti and syn diol epoxides in a 5 3 ratio (57,59). These findings are in accord with previous observations that dihydrodiols free to adopt the diequatorial conformation undergo anti stereospecific epoxidation, whereas bay region diaxial dihydrodiols yield mixtures of anti and syn diastereomers. The syn-... 

These hexacyclic hydrocarbons are generally recognized as two of the most potent unsubstituted carcinogenic PAH (38). The 3,4-dihydro-diol of dibenzo(a,i)pyrene (17) and the 1,2-dihydrodiol of dibenzo-(a,h) pyrene (lg) have been synthesized from 4-oxo-l,2,3,4-tetra-hydrodibenzo(a,i)pyrene and 1-oxo-l,2,3,4-tetrahydrodibenzo(a,h)py-rene, respectively, by Method I. (69). Treatment of these dihydro-diols with m-chloroperbenzoic acid gave the corresponding anti diol epoxides (66). 

Epoxidation of the 3,4-dihydrodiol with m-chloroperbenzoic acid afforded stereospecifically the corresponding anti diol epoxide (74). Peracid oxidation of the bay region 1,2-dihydrodiol gave a mixture of the anti and syn diol epoxide diastereomers. Assignment of the major isomer as syn was made through analysis of the NMR spectra of the acetates of the tetraols formed on hydrolysis of the individual diol epoxides (42). Peracid oxidation of the 10,11-dihydrodiol is reported to yield the corresponding anti diol epoxide (12). However, it is likely for steric reasons that the syn isomer is also formed. 

In contrast to 21, the diol epoxide derivative of the 8,9-dihydrodiol of DMBA was relatively stable. Although only the anti isomer was isolated and identified from epoxidation of the 8,9-dihydrodiol with m-chloroperbenzoic acid (84), it is likely that the syn isomer may also be formed in this reaction. The 8,9-dihydrodiol exists predominantly in the diaxial conformation as a consequence of steric interaction between the 8-hydroxyl and 7-methyl groups (88). 

The 9,10-dihydrodiol of 3-MC (24a) was synthesized from 9-hy-droxy-3-MC by Method IV (86). Oxidation of this phenol with Fremy s salt in the presence of Adogen 464, a quaternary ammonium phase transfer catalyst, furnished 3-MC 9,10-dione. Reduction of the qui-none with NaBH -C gave pure 24a in good yield. Treatment of 24a with m-chloroperbenzoic acid was monitored by HPLC in order to optimize the yield of the anti diol epoxide (25 ) and minimize its decomposition. 

Epoxidation of the 1,2- and 7,8-dihydrodiols of 5-MC with m-chloroperbenzoic acid furnished the corresponding anti diol epoxides 26 and J27. Compound 26 was the first diol epoxide bearing a methyl group in the same bay region as the epoxide function to be synthesized. While the diol epoxide 26 is relatively reactive (104), it is more stable than the structurally analogous DMBA 1,2-diol-3,4-epoxide (21) it was obtained as a white crystalline solid. 

Alkenylbenzotriazoles 865 are readily prepared by isomerization of the corresponding allyl derivatives catalyzed by Bu OK. Lithiated compounds 865 are treated with electrophiles to provide a-substituted derivatives 866. Epoxidation of the double bond with ///-chloroperbenzoic acid converts intermediates 866 into oxiranes 867 that can be hydrolyzed to furnish a-hydroxyketones 868 in good yields (Scheme 140) <1996SC2657>. 

In very recent work the [6]radialene 95 has been epoxidized with m-chloroperbenzoic acid (MCPBA) to the mono- and the bis -epoxide 168 and 169, respectively, at 0 °C, and to the tris-epoxide 170 at room temperature100. Methylenation with CH2l2/AlMe3 provides the rotaradialenes 171 and 172 (equation 21)101. Again, the relative orientation of the three-membered rings in these adducts follows from X-ray and NMR data100101. 

The required epoxy esters are obtained by reaction of the free acid (0.96 mmol) with 3,4-epoxy-3-methylbutanol (1.1 mmol), DCC (1.1 mmol), and DMAP (0.048 mmol) in CH2C12/DMF (9 1, 10 mL, 1 h at 0 °C and 2 h at r. t.). Alternatively, they can be synthesized from acid chlorides using 3-methyl-3-butenol and triethylamine (1 1 2 ratio CH2C12, 0°C), followed by epoxidation with m-chloroperbenzoic acid (1.2 equivalents, CH2C12, 0°C). 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

Alternative to m-chloroperbenzoic acid.1 This oxidant has been introduced as a suitable replacement for m-chloroperbenzoic acid, which is no longer available from commercial sources because of hazards in the manufacture. Actually MMPP is a safer reagent than MCPBA, which is shock-sensitive and potentially explosive. MMPP is soluble in water and in low-molecular-weight alcohols. The by-product, magnesium phthalate, is water-soluble and easily removed. It is generally more stable than other percarboxylic acids. It can replace MCPBA for the usual classic oxidations epoxidation, Baeyer-Villiger reactions, and oxidation of amines to N-oxides. 

The use of other peroxides in the epoxidation of glycals is limited by selectivities that are often inferior to those achieved with DMDO. One notable exception is the use of the wCPBA (m-chloroperbenzoic acid)/KF combination and its recent successful application in one-pot epoxidation alcoholysis (Scheme 5.66) [197]. This involved treatment of benzylated D-galactal 36 in dichloromethane/methanol with a mixture of wCPBA and KF (2 1) in anhydrous dichloromethane to give methyl-2-hydroxygalactoside 165. 

---