Peracid with MCPBA

Oxygenation takes place with peracids. The cyclopalladated benzylamine complex 466 is converted into the salicylaldamine complex 504 by the treatment with MCPBA[456] or /-BuO H[457]. Similarly, azobenzene is oxidized with MCPBA at the ortho position[458]. 

There are only a few reports concerning the peracid oxidation of azepines. 30% Hydrogen peroxide oxidizes TV-alkyl-6,7-dihydro-5iT-dibenz[c,e]azepines to their TV-oxides (75ZN(B)926), whereas MCPBA has been used to prepare the 3H-2-benzazepine TV-oxide (88) (74JOC2031). TV-Oxidation of 2,3,4,5-tetrahydro-lH-l-benzazepine with MCPBA is accompanied by dehydrogenation to the 4,5-dihydro TV-oxide (89) (79JOC4213). 

As peracids react very sluggishly with alcohols, it was apparent that the presence of a nitroxide was playing an important role in the oxidation of the alcohol into a ketone. This seminal serendipitous observation led to the development of the first description of the oxidation of alcohols mediated by catalytic 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) (55), published almost simultaneously by Celia et al and Ganem.3 These authors presented two papers with remarkably similar contents, in which alcohols were oxidized by treatment with MCPBA in CH2CI2 at room temperature in the presence of a catalytic amount of TEMPO (55). In both papers, a plausible mechanism is presented, whereby m-chloroperbenzoic acid oxidizes TEMPO (55) to an oxoammonium salt 56. This oxoammonium salt 56, as detailed in Ganem s paper, can react with the alcohol producing an intermediate 57, which can deliver a carbonyl compound by a Cope-like elimination. 

Enamines are susceptible to peracid oxidation, presumably through the epoxide, producing the a-hy-droxy ketone after hy lysis. Thus steroidal ketone (88) is converted via the pyrollidino enamine to the a-hydroxy derivative (89) in qiproximately 50% overall yield by treatment of the enamine with MCPBA followed by basic work up. Similar conversion of a steroidal enamide to the a>hydroxy ketone using monoperphthalic acid has been reported. 

Epoxidation of acyclic allyl alcohols with peracid and Mo/TBHP displays an opposite stereospecificity to that for the V/TBHP system. Trimethylsilyl-substituted allylic alcohols give t/zreo-epoxyalcohols with MCPBA and erythro-alcohols with VO(acac)a-TBHP, with high stereoselectivity. In the stereospecific epoxidation of cis- and trans-allyl alcohols, formation of a transition state is assumed with the development of two H bonds between the hydrogen atom of the hydroxy group of the allyl alcohol and the oxygen of the peracid, and between the hydrogen of the peracid OH and the oxygen of the ether 10. An analysis of the diastereometric transition-state interactions for stereoselective epoxidation of acyclic allylic alcohols has been published. A conformational effect may be responsible for the unexpected cis major product in Eq. 2. 

Although a, 3-unsaturated ketones are usually not oxidized with peracid, nmr data point to the formation of a cfs-bisoxirane from 20 with MCPBA (Eq.l 1). ... 

For the synthesis of oxiranes with more complex structures, the peracid method is combined with other epoxidation procedures examples are the syntheses of ( )-crotoxirane, ( )-epicrotoxirane, and ( )-isocrotoxirane ° or the preparation of cis-trioxatris-(a)homotropylidene. o-Sulfoperbenzoic acid has been used for the stereoselective epoxidation of cholesterol. The selective epoxidation of cholest-5-en-3-one too has been examined. In the synthesis of 25-hydroxycholesterol selective epoxidation occurs on and 26 is formed. The epoxidation of olefin propellanes 27 and 28 can be achieved with MCPBA. As a consequence of the secondary orbital interaction, syn-attack is more marked in the case of 28. ° Epoxypropelladiene can be synthesized in accordance with Eq. 12. ... 

Perfluoro-c -2,3-dialkyloxaziridines (64) are prepared in good yield (68-77%) by MCPBA oxidation of the corresponding perfluoroazaalkenes (188) (Equation (46)) <93JOC4754>. To be successful, the peracid needs to be > 80% pure, well-dried, and the solvent needs to be acetonitrile. Interestingly, oxidation does not proceed in CH2C12. A series of 3-/-butyl-3-( 1 -haloalkyl)oxaziridine were prepared by oxidation of the corresponding a-chloro, a-bromo, a,a-dichloro, and a,a-dibromo aldimines with MCPBA <92T7345>. 

Electrophilic Addition.—Reactions of androsta-3,5-dienes with MCPBA gave complex mixtures the composition of which was dependent upon the level of peracid used (1 or 2 equivalents). Diepoxides were isolated in low yield only when 2 equivalents were used and in general products were derived from epoxide ring opening.34 In a study of the structures of withanolides G,H,I,J,K, and U which were all shown to possess the 14a-hydroxy-group, it was demonstrated that the 14a-hydroxy-group influenced the epoxidation of the 5,6-double bond.35 Incorporation of ozonizable dyes as internal standards facilitated selective ozonization of... 

Paracyclophane (la) suflers from peracid oxidation readily oxidation of la with MCPBA proceeded at 0 °C to yield the dimer 109 quantitatively [5b], The formation of dimer 109 is explained in terms of [4 + 2] dimerization of the cyclohexadienone 108 which was formed by epoxide-carbonyl rearrangement of the initially formed epoxide 107 (Scheme 20). Naphthalenophane 55a and anthracenophane 56a (s. Scheme 13) were more reactive the MCPBA oxidation completed immediately at — 78°C to give unstable dienones 110 and 111 (Structures 21) [50]. 

We screened our libraries for the site-selective epoxidation of famesol (120) [182]. Either the peracid reagent /mCPBA, or catalytic n-alkyl acids, provided a benchmark for the intrinsic and poorly selective product distribution of monoepoxides (see Fig. 13b inset for schematic of famesol nomenclature). Hits from the initial libraries, however, showed selectivity toward 2,3-epoxide 121 and 6,7-epoxide 122, inspiring the development of biased combinatorial libraries to select further for these oxidation sites (Fig. 13b). Further optimization of the sequences after additional library sequences yielded peptide 123, which provided 2,3-epoxy famesol 121 with 1 1 >100 site selectivity (10,11 6,7 2,3) in 81% yield and 86% ee. These values are comparable to those provided for this substrate by the venerable Sharpless asymmetric epoxidation [187]. Optimization of the 6,7-biased sequence led to peptide 124, which provided 6,7-epoxy famesol 122 in 1.2 8.0 1.0 site selectivity (10,11 6,7 2,3) in 43% yield and 10% ee. Despite the modest ee of 122, we note that, to our knowledge, no existing catalytic epoxidation method is capable of providing 122 directly in reasonable purity. 

The common peracids used are perbenzoic acid, performic acid and m-chloroperbenzoic acid. The reaction is generally carried out in organic solvents. The Baeyer-Villiger oxidation of ketones has been satisfactorily carried out in aqueous heterogeneous medium with MCPBA at room temperature. Some examples using the above methodology are given (Scheme 81). 

Vinylepoxides can be obtained by various strategies, all with their inherent limitations. Racemic epoxidation of olefins is a straightforward route to epoxides, as pure trans- or cis-epoxides can be obtained from ( )- or (Z)-alkenes, respectively. Various oxidants - such as mCPBA and other peracids, H2O2, or VO(acac)2/TBHP - can all be employed in this transformation [1],... 

The oxidation of 3,4-di-/i m-butylthiophene 1,1-dioxide with peracids (MCPBA or trifluoroperacetic acid) affords the corresponding sultone in only moderate yield <1991JOC4001>, though the sultine intermediate could be isolated and characterized structurally. 

Peracids form as transient species from the oxidation of benzaldehyde during autoxidation. For convenience we have chosen m-chloroperbenzoic acid (MCPBA) as our oxidant since this would be similar to the peracid formed from the very important intermediate 4-carboxybenzaldehyde formed during the oxidation of p-xylene (2). MCPBA would be formed in very low concentrations during oxidation hence we normally study the reaction of MCPBA with an excess of catalyst components i.e. MCPBA < pseudo first order conditions). The sequence of reactions that occurs when MCPBA is reacted with Co(II), Mn(II), and HBr has been previously discussed by Jones (9) in the presence of 5% water in acetic acid. We have repeated much of this work in 10% HjO/HOAc solutions and in general agree with his findings when one accounts for differences in temperatures, concentrations, and water concentrations. 

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