DMDO

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

A retroaldol fragmentation subsequent to the addition of p-TsOI I and a small amount of water to epoxide 206, obtained by oxidation of enol ether 205 with DMDO, resulted in the direct formation of dialdehyde hydrate 208, possessing the spirostructure necessary for the construction of the fused-rings core of ( )-ginkoli-de B. Apparently, hydrolysis of the epoxide produces the hemiacetal 207, which undergoes retroaldol fragmentation of the cydobutane to afford the dialdehyde, which forms the stable hydrate 208 (Scheme 8.52) [94]. 

Dimethyldioxirane DMDO discovered by Murray and coworkers, is a superior choice for the epoxidation of most olefins, giving comparable or higher yields than m-CPBA-based epoxidation [21]. Proceeding rapidly under neutral and mild conditions, it is especially well suited for the synthesis of sensitive epoxides of enol esters, enol lactones [22], and enol ethers [23]. The reaction is stereospecific, gen-... 

Epoxidation by Dioxirane Derivatives. Another useful epoxidizing agent is dimethyldioxirane (DMDO),86 which is generated by in situ reaction of acetone and peroxymonosulfate in buffered aqueous solution. Distillation gives about aO.lM solution of DMDO in acetone.87... 

Higher concentrations of DMDO can be obtained by extraction of a 1 1 aqueous dilution of the distillate by CH2C12, CHC13, or CC14.88 Another method involves in situ generation of DMDO under phase transfer conditions.89... 

The yields and rates of oxidation by DMDO under these in situ conditions depend on pH and other reaction parameters.90... 

Similarly to peroxycarboxylic acids, DMDO is subject to cis or syn stereoselectivity by hydroxy and other hydrogen-bonding functional groups.93 However a study of several substituted cyclohexenes in CH3CN —H20 suggested a dominance by steric effects. In particular, the hydroxy groups in cyclohex-2-enol and... 

Other ketones besides acetone can be used for in situ generation of dioxi-ranes by reaction with peroxysulfate or another suitable peroxide. More electrophilic ketones give more reactive dioxiranes. 3-Methyl-3-trifluoromethyldioxirane is a more reactive analog of DMDO.99 This reagent, which is generated in situ from 1,1,1-trifluoroacetone, can oxidize less reactive compounds such as methyl cinnamate. 

The epoxidation can be done either with peroxy acids or DMDO. In the former case, the rearrangement is catalyzed by the carboxylic acid that is formed, whereas with DMDO, the intermediate epoxides can sometimes be isolated. 

The yield in the metathesis reaction was 80% and was followed by a Lindlar reduction. The synthesis was completed by epoxidation with DMDO. 

Upon treatment with dimethyldioxirane (DMDO), benzannulated dihydropyrrolizine 84 afforded two dimers 86 and 86, each as a mixture of two diastereomers < 1997JA1159>. The zwitterionic species 85 is postulated as intermediate in these dimerizations (Scheme 10). 

Reaction of dihydropyrrolizine 87 with DMDO in aqueous acetone gives the oxidative rearrangement compound 88 in 59% yield <20030L785>. A plausible mechanism was proposed as shown in Scheme 11. 

Scheme 5.65 Summary of reaction outcomes in DMDO epoxidation of glycals.

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. 

Polymer-supported glucal 37 was converted to the protected thioethyl glucosyl donor 39 as outlined in Scheme 2.11. Compound 37 was first epoxidized by the action of DMDO. The resulting 1,2-anhydrosugar was opened by a mixture of ethanethiol and dichloromethane (1 1) in the presence of a trace of trifluoroacetic acid. Polymer-bound 38 was thus obtained in 91% yield. This was a substantial improvement over the 78% yield obtained by the same protocol in solution. Protection by reaction with pivaloyl chloride occurred in quantitative yield to furnish 39a. 

The first problem to be addressed in the solid-phase assembly of Leb involved the synthesis of the core tetrasaccharide (Scheme 2.17).25 Polymer-bound galactal 10 was epoxidized with DMDO. The resultant epoxide reacted with a solution of glucal 55 to give polymer-bound disaccharide diol 56. This reaction proceeded in a highly regioselective fashion, wherein glycosylation occurred only at the allylic C3 position... 

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