Dithiane oxides synthesis

One-pot stereocontrolled cycloalkanone synthesis using dithiane oxides... 

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. - ... 

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

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... 

Direct oxidation of A9-THC at position C-11 involves mainly an isomerization to A8-THC another opportimity in the synthesis of A9-THC-metabolites is the pretreatment of terpenoid synthons by introduction of protective groups, e.g., 1,3-dithiane (6.1 in Fig. 6) followed by the condensation with olivetol (6.2) [76]. The formed product is a protected derivate... 

Page et al. (see [298] and references therein) have shown that generally excellent stereocontrol in organic reactions can be obtained by using DITOX (1,3-dithiane-l-oxide) derivatives as chiral auxiliaries. The one-pot stereo-controlled cycloalkanone synthesis given here outlines some aspects of the chemistry worked out for efficient acylation-alkylations steps. Of note are the use of N-acyl imidazoles under mixed base (sodium hexamethyldisilazide/n-butyllithium) conditions to yield the lithium enolates of 2-acyl-l,3-dithiane-l-oxides) and the sequential alkylation-cyclization of the latter (steps (iv) and (v)). 

As is often found in asymmetric synthesis, temperature is an experimental parameter that can increase enantioselectivity. Here, however, a decrease in the reaction temperature does not always increase the enantioselectivity. An optimum temperature was found to be -20°C to -25°C for the oxidation of methyl p-tolyl sulfide [17], and this temperature range was retained for the standard oxidations. In the case of the monooxidation of dithianes, the maximum enantioselectivity was obtained at ca. —40°C [29] (Scheme 6C.1). 

Both enantiomers of the 2-ethyl- 1,3-dithiane-l -oxide starting material may be prepared selectively in up to optical purity. The aminated products are of interest as potential synthons for chiral synthesis of both enantiomers of a-amino acids. 

A number of catalytic reactions studied by Russian authors are necessarily left out of this review. These include nitration and sulfona-tion (138). As an example the use of alumina in the synthesis of heterocyclic compounds may be mentioned. Ethylene oxide with ammonia gave pyridine with hydrogen sulfide about 20 % thiophene was formed at 300-450° (211). At 200°C. ethylene oxide and hydrogen sulfide gave thioxane and dithiane (212,429). Yur ev developed conditions under which the hetero atom of furan, thiophene, and pyrrole could be interchanged (425,426,427,428). 

Since 1987 our group has been concerned with the design, synthesis, development, and more recently the application of dithiane 1-oxide derivatives as asymmetric building blocks for organic synthesis. This review focuses on the development of highly diastereoselective reactions, principally carried out at the acyl side chain of 2-acyl dithiane 1-oxide derivatives (1). 

We have subsequently extended our studies to include the enantioselective synthesis of a wide range of 2-substituted-1,3-dithiane 1-oxides,68 including 2-heterosubstituted-1,3-dithiane 1 -oxides.69... 

A new synthesis of the pyran (251), confusingly named linaloyl oxide, has been reported. 2,6-Dimethyl-l,2-epoxyhept-5-ene gave (252) with 2-lithio-l,3-dithian almost quantitatively, and boron trifluoride-catalysed cyclization to (253) readily led to (251).353... 

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