Dimethyldioxirane, nucleophilic reactions

The reaction of allenes with peracids and other oxygen transfer reagents such as dimethyldioxirane (DM DO) or hydrogen peroxide proceeds via allene oxide intermediates (Scheme 17.17). The allene oxide moiety is a versatile functionality. It encompasses the structural features of an epoxide, an olefin and an enol ether. These reactive intermediates may then isomerize to cyclopropanones, react with nucleophiles to give functionalized ketones or participate in a second epoxidation reaction to give spirodioxides, which can react further with a nucleophile to give hydroxy ketones. 

Only a few isolated allene oxides have been synthesized from allenes and characterized. Most often peracids are used but the oxidative and acidic conditions usually result in a complex mixture of products. To overcome this problem, dimethyldioxirane (DMDO) can be used, which rapidly oxidizes allenes to spirodiepoxides. Several synthetically useful methods have been developed via in situ reaction of the intermediate allene oxide or spirodioxide with different nucleophiles. 

Another example of nucleophilic attack of anilines at an oxygen atom has been reported by Buxton and coworkers134. The oxidation of 4-substituted /V,/V-dimethylanilines by dimethyldioxirane, 13, in acetone showed a similar qualitative trend as those for the reactions at the Mel and benzoyl peroxide reactions with a reactivity decrease in the order X = MeO > H > Cl N02. These trends suggest that the oxidation of DMAs by 13 is electrophilic. The px value of —0.89 shows similarity to the values in the reactions of DMAs with Mel (Menschutkin reaction) which has a px value of —3.30 at 35 °C in 90% aqueous acetone. While in the latter reactions the TS is thought to have developed almost a full positive charge, the reactions with 13 have much less charge development partially due to steric crowding in the TS (Scheme 17). 

A useful conversion of a nucleoside 2,6-dithione into a 6-methylamino-adenosine via oxidation with dimethyldioxirane, illustrates several instructive points. The presumed intermediates are sulfinic acids the 2-sulfinic acid loses sulfur dioxide to leave hydrogen at C-2, and nucleophilic displacement of the 6-sulfinic acid (or possibly the sulfonic acid after further oxidation) introduces the amino group. Similar reactions can be carried out on pyrimidine thiones. The scheme shows intermediates derived from a disulfinic acid - it is not clear in what order oxidations/loss of sulfur dioxide/displacements take place. 

The cleavage of heteroaryl sulfones from polymeric supports can be achieved by reaction with azide ions. Suckling el al. applied this strategy to the synthesis of pteridines. In fact, the starting pyrimidine was linked to polystyrene via a thioether 214. After con-stmction of the pteridine ring system, the activation of the sulfur linker by oxidation to the sulfone with dimethyldioxirane followed by nucleophilic substitution with sodium azide affords the target molecule 218 in 41% overall yield (Scheme 3.30). 

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