Oxidative dithianes

Oxathiane and -dithiane are formed from ethylene oxide and hydrogen sulfide at 200°C in the presence of an aluminum oxide catalyst (65). 

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

HgCl2, CaC03, THF, H2O, 0°, rapid. These derivatives are less susceptible to oxidation and hydrogenolysis than are the 1,3-dithiane and 1,3-dithiolane precursors. 

The Dim ester was developed for the protection of the carboxyl function during peptide synthesis. It is prepared by transesterification of amino acid methyl esters with 2-(hydroxymethyl)-l,3-dithiane and Al(/-PrO)3 (reflux, 4 h, 75°, 12 torr, 75% yield). It is removed by oxidation [H2O2, (NH4)2Mo04 pH 8, H2O, 60 min, 83% yield]. Since it must be removed by oxidation it is not compatible with.sulfur-containing amino acids such as cysteine and methionine. Its suitability for other, easily oxidized amino acids (e.g., tyrosine and tryptophan) must also be questioned. It is stable to CF3CO2H and HCl/ether. - ... 

This method for the preparation of cyclobutanone via oxaspiropentane is an adaptation of that described by Salaiin and Conia. The previously known large-scale preparations of cyclobutanone consist of the reaction of the hazardous diazomethane with ketene, the oxidative degradation or the ozonization in presence of pjrridine of methylenecyclobutane prepared from pentaerythritol, or the recently reported dithiane method of Corey and Seebach, which has the disadvantage of producing an aqueous solution of the highly water-soluble cyclobutanone. A procedure involving the solvolytic cyclization of 3-butyn-l-yl trifluoro-methanesulfonate is described in Org. Syn., 54, 84 (1974). 

Electrolysis 1.5 V, CH.CN, H2O, LiC104 or Bu4N+C104 , 50-75% yield. " 1,3-Dithiolanes were not cleaved efficiently by electrolytic oxidation. This method has been applied to dithiane deprotection to produce a-diketones. ... 

Dithiane 1-oxide derivatives as chiral auxiliaries and asymmetric building blocks for organic synthesis 980PP145. 

Enantioselective oxidation of 1,3-dithianes to corresponding S-oxides and S,S-dioxides by designer yeast 99JHC1533. 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

To create a setting favorable for the formation of the E-ring of ginkgolide B, it is first necessary to modify the reactivity potential of ring F in 23. Exposure of a solution of 23 in methylene chloride to 1,3-propanedithiol and titanium(iv) chloride at 0°C results in the formation of dithiane 24 in quantitative yield. Oxidation of the primary alcohol with PDC in the presence of acetic acid gives aldehyde 25 in a yield of 75 %. 

When a solution of 25 in a 1 1 mixture of methanol and methylene chloride is exposed to periodic acid, the dithiane group is cleaved oxidatively to give, after treatment of the crude product with camphorsulfonic acid (CSA) in methanol, bisacetal 12 as a 2 1 mixture of C-12 anomers in a yield of 80% (Scheme 3). Although the conversion of 12 into 10 could be carried out on the mixture of anomers, it was found to be more convenient to carry each isomer forward separately. When 12 is treated with lithium diethylamide, the methine hydrogen adjacent to the lactone carbonyl is removed as a proton to give an enolate which is then oxidized in a completely diastereoselective fashion with Davis s oxaziridine18 to afford 11. 

Besides 1,3-oxathianes, the 1,3-dithiane 1-oxide moiety can be used for directing the nucleophilic addition of an organometallic reagent to a carbonyl group in a diastereoselective manner. The addition of methylmagnesium iodide to the 2-acyl-l,3-dithiane 1-oxide 23A leads exclusively to the diastereomer which is formed by Re-side attack. On the other hand, addition... 

A mixture of 2-methyl-2-trimethyIsilyl-l,3-dithiane (121 mmol), mercury(n) chloride (266mmol), and mercury(u) oxide (181 mmol) in methanol (225 ml) and water (25 ml) was stirred vigorously and heated under reflux for 2 h. It was then cooled and filtered, and the precipitate was... 

Carlson and Helquist410 were the first to perform the alkylation of 2-lithio 1,3-dithian-S-oxide 323 (equation 180). The yields of this reaction appeared, however, to be low. In spite of the fact that dithian-S-oxides have been intensively investigated268-411, their synthetic applications are rather limited. 

The use of ethyl ethylthiomethyl sulphoxide in this reaction leads to the desired addition products in much better yields (95-97%). These products were then converted into ketene dithioacetal monoxide derivatives 430 by a sequence of reactions (equation 258)505. Reaction of 2-lithio-l,3-dithiane-l-oxide with benzophenone affords a mixture of the diastereoisomeric tertiary alcohols 431 in a ratio which is temperature dependent (cis trans changes from 3 1 at — 78 °C to 1 1 at room temperature)268. 

It is noteworthy that, based on the sulfoxide- sulfenic acid rearrangement, the readily accessible 1,3-dithiolane systems (316) may be utilized (equation 116) as an efficient entry into the 1,4-dithiane series303, including the construction of carbocyclic fused systems304. The oxidation of the dithienes 318 to the corresponding sulfoxides (319 and 320) and sulfones is a simple, straightforward process. 

The molecular mechanics method314 has been applied to the calculation of conformational properties of the thiane, dithiane and trithiane oxide systems315, which are... 

The same preferences have been calculated315 and observed319 in the 1,2-dithiane oxide system. Although the chair forms are also more stable than the twist or boat in 1,3-, 1,4-dithianes and 1,3,5-trithianes, the preference of the oxygen is highly variable, depending on steric and electronic interactions. 

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