Oxidation with Dimethyldioxirane

This ether, developed for the protection of a pyranoside anomeric hydroxyl, is prepared via a Konigs-Knorr reaction from the glycosyl bromide and 2-(ben-zylthio)ethanol in the presence of DIPEA. It is cleaved, after oxidation with dimethyldioxirane, by treatment with LDA or MeONa. ... 

The most widely employed methods for the synthesis of nitrones are the condensation of carbonyl compounds with A-hydroxylamines5 and the oxidation of A+V-di substituted hydroxylamines.5 9 Practical and reliable methods for the oxidation of more easily available secondary amines have become available only recently.10 11 12 13. These include reactions with stoichiometric oxidants not readily available, such as dimethyldioxirane10 or A-phenylsulfonyl-C-phenyloxaziridine,11 and oxidations with hydrogen peroxide catalyzed by Na2W044 12 or Se02.13 All these methods suffer from limitations in scope and substrate tolerance. For example, oxidations with dimethyldioxirane seem to be limited to arylmethanamines and the above mentioned catalytic oxidations have been reported (and we have experienced as well) to give... 

Acetyl-protected 1,2,3,4-tetrahydropyrazines 105, which are prepared by treatment of 2,3-dihydropyrazine with acetic anhydride and zinc (Scheme 27), undergo photooxidation to produce new dioxetanes 106 <1995JA9690>. Upon thermolysis, the dioxetanes 106 decompose quantitatively to tetraacyl ethylenediamines 107. Dimethyldioxirane oxidation of tetrahydropyrazine 105 affords novel epoxide 108, which is also generated by deoxygenation of dioxetane 106 with dimethyl sulfide. In 2,3,4,5-tetrahydropyrazine 1-oxide 109, which is prepared... 

The oxidation of picolinaldehydes to the corresponding Af-oxides with dimethyldioxirane proceeds in good yield without the need to protect the aldehyde function <99T12557>. The urea-hydrogen peroxide complex oxidizes pyridines to pyridine Af-oxides <990L189>. 

Two new reactive, very powerful organic peroxides, dimethyldioxirane and methyl(trifluoromethyl)dioxirane (4), have been introduced.81-83 The latter is more reactive and can be used more conveniently.84 85 Acyclic alkanes give a mixture of isomeric ketones on oxidation with methyl(trifluoromethyl)dioxirane,84,85 while cyclohexanone is the sole product in the oxidation of cyclohexane (99% selectivity at 98% conversion).85 With the exception of norbomane, which undergoes oxidation at the secondary C-2 position, highly selective tertiary hydroxylations can be carried out with regioselectivities in the same order of magnitude as in oxidations by peracids.85-87 A similar mild and selective tertiary hydroxylation by perfluorodialkyloxaziridines was also reported.88 Oxidation with dioxiranes is highly stereoselective 85... 

Dioxiranes constitute a new class of organic peroxides that possess great potential as oxidants with a variety of applications in synthetic organic chemistry.5 7 A new convenient route for the synthesis of silanol polymers has been developed by the selective oxidation of =Si—H bonds with dimethyldioxirane. A series of styrene-based silanol polymers and copolymers were synthesized (Scheme l).8 9 The precursor polymers and styrene copolymers containing =Si—H bond were first synthesized by free radical polymerization of the corresponding monomers or copolymerization of the... 

Tertiary amine oxides can be converted into TV-hydroxy secondary amines provided that one of the TV-substituents can be selectively eliminated. This procedure has been applied to the synthesis of secondary A-hydroxy-a-amino acids 34 from the corresponding secondary a-amino acids using the /V-cyanoethyl group for transient protection of the secondary amine (Scheme 10) J40l More recently, direct oxidation with 2,2-dimethyldioxirane of a primary amine has been described for H-L-Val-OMe (82% yield) and H-L-Phe-OMe (54% yield))13 The reaction proceeds smoothly without epimerization, but no experimental details have been reported. 

Dimethyldioxirane oxidizes acyclic vinylsilanes at room temperature to the corresponding epoxides 166 in excellent yield (equation 141)255. Allylic oxidation is found in appreciable amounts when cyclic vinylsilanes are used. It is interesting to note that simple alkenes react faster with dioxirane than vinylsilanes. The trend appears to be reversed when MCPBA is employed as the oxidant. 

By H NMR monitoring of the oxidation of benzene oxide-oxepine with dimethyldioxirane (DMDO), a significant by-product, oxepine 4,5-dioxide, was identified <1997CRT1314>. This fact supports the hypothesis that the route from oxepine to muconaldehyde proceeds via oxepine 2,3-oxide with a minor pathway leading to symmetrical oxepine 4,5-oxide. The DMDO oxidations provide model systems for the cytochrome P450-dependent metabolism of benzene and atmospheric photooxidation of benzenoid hydrocarbons. 

Deoxygenation of pyridine A-oxides has been achieved using dimethyldioxiran <95CC1831> and palladium with sodium hypophosphite <95GCI(124)385>. Pyridine A-oxides, with ruthenium porphyrin catalysts, have been used as an oxidant of aromatic compounds <95JA(117)8879> or olefins, alcohols, sulfides and alkanes <95FI(40)867>. 

Arene dioxides. Arene dioxides have not been identified as metabolites of polycyclic arenes, but some identified metabolites may be formed from arene dioxides. Arene dioxides can be obtained by reaction of polyarenes containing a double bond comparable to the 9,10-double bond of phenanthrene (such as 2) by oxidation with dimethyldioxirane (1), but in modest yield. The dioxide S cannot be obtained by this method, but can be obtained via a tramwic-bromoacetate.1... 

The l,5-dioxaspiro[3,2]hexane (42) has been shown to be a useful precursor for both aminodiol and aminotriol sphingoid bases. The synthesis of oxetane (42) started with serine via a Mitsunobu lactone formation followed by sequential titanium-mediated methylenation and oxidation with dimethyldioxirane <02OL1719>. 

The first synthesis of CR)-4,5-dihydro-37/-dinaphtho[2,l- l, 2 -< ]selenepin oxide 81 has been described by Procter and Rayner via the oxidation of the novel C2-symmetrical selenide 80 with MCPBA <2000SC2975>. In comparison, conversion of the 1,3-diselenetane 82 to the diselenoxide 68 was performed in a high yield by oxidation with dimethyldioxirane <2000JOC1799>. 

Reactions which formally involve the oxidation of azides have been reviewed by Boyer. Other oxidations with useful synthetic applications include two which start from nitrogen ylides. Sulfimides (50) derived from electron-deficient aromatic and heterocyclic amines are oxidized to the corresponding nitroso compounds by MCPBA. > This is a very useful method of preparation of some otherwise inaccessible nitroso compounds such as 2-nitrosopyridine and 1-nitrosoisoquinoline. They can be further oxidized, for example by ozone, to the nitro compounds. Phosphimides (51) are oxidized directly by ozone to the nitro compounds, although the nitroso compounds are intermediates. Isocyanates can also be oxidized to the corresponding nitro compounds, by dimethyldioxirane (1). ... 

While many of the remaining steps to convert 320 to FR900482 are simple functional group transformations, it is worthwhile to look at some of these steps as examples of reactions that can be undertaken in the presence of an aziridine. Compound 320 is converted to 321 through a series of deprotection, oxidation, and N-protection. The enolate of 321 is treated with formaldehyde to generate 322 as a seperable 1 1 mixture of diastereomers. The unwanted diastereomer could be converted to a 70 30 mixture of diastereomers by treatment with DBU in toluene. The hydroxyl of 322 was protected and then the compound was oxidized with dimethyldioxirane (DMDO) to provide intermediate W-oxide 323. Loss of anisaldehyde followed by intramolecular cyclization provided the tetracyclic 324 (Scheme 63). This compound was then converted to FR900482. 

The method is also successful for carboxyhc esters , and A,A-disubstituted amides, and can be made enantioselective by the use of a chiral oxaziridine. Dimethyldioxirane also oxidizes ketones (through their enolate forms) to a-hydroxy ketones. Titanium enolates can be oxidized with tert-butyl hydroperoxide or with dimethyl dioxirane and hydrolyzed with aqueous ammonium fluoride to give the a-hydroxy ketone. Ketones are converted to the a-oxamino derivative (0=C CH2- 0=C CHONHPh) with excellent enantioselectivity using... 

Similar oxidants are used for epoxidation of esters of unsaturated carboxylic acids. Methyl oleate is oxidized with peroxybenzoic acid [295] or peroxylauric acid [174] to methyl 9,10-epoxystearate acid in respective yields of 67 and 76%. Alkaline 50% hydrogen peroxide in methanolic solution transforms diethyl ethylidenemalonate at pH 8.5-9.0 and at 35-40 C over a period of 1 h into ethyl 2-ethoxycarbonyl-2,3-epoxybutyrate in 82% yield [145], A somewhat exotic oxidizing agent, dimethyldioxirane, converts ethyl tra/u-cinnamate into ethyl 2,3-epoxyhydrocinnamate in 63% isolated yield [210]. 

There are other oxidants reported. The combination of m-CPBA and N-me thy I-morpholine-N-oxide is an effective anhydrous oxidant system for enantioselective oxidation with Mn(salen) compounds [224,225]. Dimethyldioxirane is prepared by the reaction of Oxone (potassium monoperoxysulfate) with acetone [317] and is a member of the smallest cyclic peroxide system. It is an active oxidant for a variety of olefins [318,319]. 

The activating a-phenylthio group can then be removed either by oxidation with dimethyldioxirane followed by thermolysis to afford the isoflavones or through reduction by nickel boride to give the corresponding isoflavanones. ... 

Dioxiranes, three-membered-ring cyclic peroxides, are known as highly efficient and selective oxidants, capable of performing a variety of transformations for synthetic purposes. It is known that some reactions of these peroxides are accompanied by chemiluminescence due to the release of singlet oxygen. For instance, infra-red chemiluminescence (IR-CL) of O2 at A, 1270 nm is emitted in the reaction of tertiary amines and N-oxides with dimethyldioxirane (DMD) and methyl(trifluoromethyl)dioxirane (TFD), as well as during the anion-catalyzed breakdown of the dioxiranes. Furthermore, IR-CL emission is produced in the ketone-catalyzed decomposition of the monoperoxysulfate ion HSOs through the intermediary dioxirane. ... 

Scheme 2. Dimethyldioxirane oxidation of substrates with electron donors (ED)...

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