Ethers oxidation with dioxirane

For most of these operations, isolated dioxirane solutions are more convenient, because simpler work-up procedures are involved. Furthermore, hydrolytically and acid/base-sensitive substrates may be employed, because the reaction is conducted under strictly anhydrous and neutral conditions. Solvents inert toward dioxirane oxidation may be used for dilution purposes in these oxidations, which include acetone, butanone, cyclohexanone, CH2C12, CHC13, CC14, benzene, and CH3CN. Alcohols (except t-BuOH) and ethers normally should be avoided as solvents, because they react slowly with dioxiranes, especially TFD [37]. 

Oxidation of cyclic enol ether 35 with dimethyl dioxirane (DMDO) followed by in situ reduction of the intermediate epoxide with DIBALH gave secondary alcohol as a 10 1 mixture of diastereom-ers. Oxidation of these alcohols with TPAP/NMO afforded a 10 1 mixture of ketone 37 and its C16 epimer. The isomers were separated and the minor isomer was recycled to a 4 1 mixture of isomers by treatment with imidazole. Subsequent construction of the D-ring was performed by radical reduction of mixed thioacetal in the same way as that adopted by the Sasaki group, leading to octacycle 38. Stereoselective installation of the triene side chain was then carried out via (Z)-vinyl iodide 39... 

The ozonolysis of ethylene in the liquid phase (without a solvent) was shown to take place by the Criegee mechanism.This reaction has been used to study the structure of the intermediate 16 or 17. The compound dioxirane (21) was identified in the reaetion mixture at low temperatures and is probably in equilibrium with the biradical 17 (R = H). Dioxirane has been produced in solution but it oxidatively cleaves dialky] ethers (such as Et—O—Et) via a chain radical process, so the choice of solvent is important. 

It should finally be pointed out that the mild reaction conditions typically employed in dioxirane-mediated oxidations enable the asymmetric epoxidation of enol ethers and enol esters. With the silyl ethers, work-up provides enantiomeri-cally enriched a-hydroxy ketones. As summarized in Table 10.1, quite significant enantiomeric excesses were achieved by use of catalyst 10 at loadings ranging from 30 [30] to 300 mol% [31]. Enol esters afford the intact acyloxyepoxides enantiomeric purities are, again, quite remarkable. 

The highly potent antithrombotic (+)-rishirilide B was synthesized in the laboratory of S.J. Danishefsky. One of the tertiary alcohol functionalities was introduced via the Rubottom oxidation of a six-membered silyl dienol ether with dimethyl dioxirane (DMDO). The oxidation was completely stereoselective, and it was guided by the proximal secondary methyl group. Subsequently, the enone was converted to the enedione, which was used as a dienophile in the key intermoiecuiar Dieis-Aider cycioaddition step. 

Adam, W., Fell, R. T., Saha-Moller, C. R., Zhao, C.-G. Synthesis of optically active a-hydroxy ketones by enantioselective oxidation of silyl enol ethers with a fructose-derived dioxirane. Tetrahedron Asymmetry 1998, 9, 397-401. 

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. 

Excellent reviews on dioxirane-mediated oxidations have appeared. One of the most eharacteristic points is that dioxiranes can be applied to the epoxidation of labile olefins such as enol ethers, enol acrylates, allenes and others. Dioxiranes have also been utilized for phenolic oxidation, but in relatively rare cases. Oxidation of simple phenols and anisoles with dimethyldioxirane (544) provided only a complex mixture, so that hindered phenols are more favorable. On treatment with dimethyldioxirane (4 equiv.) in acetone, 2,4-di(terf-butyl)phenol (216) was oxidized to afford in 79% yield the corresponding o-benzoquinone 220, which reacted with 544 and aq. NaHS03 to give catechol 545. Dimethyldioxirane-promoted oxidation of 545 provided again a quantitative yield of 220. Further oxidation of 220 produced a 52% yield of two epoxides 546 and 547 in a ratio of 1 20. Oxidation of thymol (548) was effected with dimethyldioxirane in acetone to afford fhe four oxidation producfs 549-552 in 10, 20, 10 and 10% yields, respectively (Scheme 102). ... 

Several years ago we presented evidence that the oxidation of a variety of organic compounds (hydrocarbons, alcohols, ethers, aldehydes, etc.) by peracids [20] and dioxiranes [21] could be explained by radical mechanism, in contrast with the... 

Several methoxy-substituted benzyl etbers have been prepared and used as protective groups. Tbeir utility lies in tbe fact that they are more readily cleaved oxidatively than tbe unsubstituted benzyl etbers. These etbers are not stable to metbyl(trifluorom ethyl)dioxirane, which oxidizes the aromatic ring. The relatedp-(dodecyloxy)benzyl ether has been prepared to facilitate chromatographic purification of carbohydrates on Ci8 silica gel. The table below gives the relative rates of cleavage with dichloro-dicyanoquinone (DDQ). ... 

While ethers react only slowly with dimethyldioxirane, they are efficiently hydroxylated by methyl(trifluoromethyl)dioxirane even at low temperatures. Thus r-butyl methyl ether [32] was converted to f-butyl alcohol through its hemiacetal. On the other hand, tetrahydrofuran gave butyrolactone [32] in which presumably the intermediary cyclic hemiacetal was oxidized to the lactone by an additional C —H insertion. The ketal was degraded into 2-butanone and the orthoformate into diethyl carbonate [32]. The latter transformation may serve useful for deketalation under neutral conditions. 

Paquette, L.A. Kreilein, M.M. Bedore, M.W. Friedrich, D. Oxidative cleavage of p-methoxybenzyl ethers with methyl(trifluoromethyl)dioxirane. Org. Lett. 2005, 7,4665. 

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