Oxathianes reduction

Using oxathiane 11, ( + )-(i )-2-methoxy-2-phenylpropanoic acid was obtained in 97% ee, however, the synthesis contains some inconvenient reaction steps. Thus, reduction of ( + )-10-camphorsulfonic acid (8) leads in low yield to a mixture of 10-mercaptoisoborneol (9 A) and 10-mercaptoborneol (9B) which must be separated by chromatography. The oxathiane 10 resists deprotonation with butyllithium and, therefore,, y -butyllithium had to be employed. Furthermore, after addition of methylmagnesium iodide, cleavage of the oxathiane moiety 12, with iodomethane did not proceed as well as with the simpler oxathianes 3. 

Benzyltriethylammonium tetrathiomolybdate, [BnNEt3]2MoS4, is a useful sulfur transfer reagent which has now been shown to effect a one-pot, three-step sequence of S-transfer— reduction—Michael addition. The intramolecular version successfully produces 1,4-oxathianes from the bromoenone 108 (Scheme 65). In like manner, the bicyclo[3.3.1]nonane skeleton incorporating a thiopyran ring can be constructed . 

Another type of heterocycle containing two heteroatoms susceptible of being cleaved reductively are 1,3-dioxanes or 1,3-oxathianes 422. They were treated with lithium and a catalytic amount of DTBB (4.5%) in THF at room temperature (Y = O) or at —78 °C (Y = S) to yield, after hydrolysis with water, functionalized homobenzylic alcohols 425 (Scheme 119) . The participation of intermediates 423 and 424 has been postulated in order to explain the obtained results. 

A reversal of the stereochemical outcome of the reduction of 2-acyl-l,3-oxathianes was demonstrated when the 1,3-oxathiane 3-oxide instead of 1,3-oxathiane was treated with chelating reducing agents, such as L-selectride (Equation 63) <1998BKC911>. 

The desulfurization of 1,4-oxathiane with sodium in refluxing hydrocarbon solvent, which allows the formation of diethyl ether in very good yield (>95%), can be reported here <1998TL2671>. Furthermore, 6-hydroxy-1,4-benzodithiin undergoes a reductive cleavage with lithium in liquid ammonia, provided the 3,4-dimercaptophenol <2004BML3753>. 

Hydrolysis of the 1,3-oxathiane moiety has been accomplished under mild conditions (0°C, 5 min) by the use of N-Chlorosuccinimide-Silver(l) Nitrate. This oxidative hydrolysis produces a-hydroxy aldehydes in good yields and, in addition, two diastereomeric sultines (19) (eq 8). The use of Iodine-for the oxidative hydrolysis of 1,3-oxathianes has also recently been reported. The tertiary a-hydroxy aldehydes are easily oxidized directly to the acids (Sodium Chlorite) or methyl esters (MeOH, I2, KOH) or are conveniently reduced to the diols by direct reduction of the hydrolysis mixture with Sodium Borohydride. The secondary a-hydroxy aldehydes could likewise be reduced to the glycols without racemization however, oxidation required pro-... 

Table 13 Reductions of Oxathiolanes and Oxathianes with Calcium in Liquid Ammonia " ...

The reduction of 2-acyl- 1,3-oxathianes such as 3.96 (X = S) or of 2-acyl-3-oxa-N-benzylpiperidines 3.96 (X = NCH2Ph) can also take place with or without chelation control [El, EFl, EH2, KEl, KF4]. In cases of chelation control, the oxygen atom of the heterocycle participates in the chelation process (Figure 3.32). When the reaction is carried out with Li(5-Bu)3BH in the presence of Lil as an additive, the reduction occurs under chelation control. However, when using two equivalents of DIBAH, each of them coordinates to a one basic site, and no chelation takes place. The use of these chiral auxiliaries allows the synthesis of nonracemic a-hydroxyaldehydes or a-hydroxyesters with a high enantiomeric excess [NNl, S3]. 

The presence of a chiral acetal, aminal or oxathiane in the vicinity of a carbonyl group can direct the reduction of a ketone toward a diastereoisomeric alcohol, whether or not chelation is operative. For example, the LiAlHf or Li 5-BU3BH reductions shown in Figure 6.13 give predominantly the diastereoisomer predicted by the Felkin-Ahn model while reductions with DIBAL or LiAlH4/MgBr2 give predominantly the diastereoisomer predicted by the chelation model [87,94, 213, 226],... 

The products obtained by the action of peracids upon 3-alkoxy-3,5-dienes are dependent upon the reaction conditions. Aqueous organic solvents and the gradual addition of peracid favour the formation of 6 -hydroxy-4-en-3-one, but when an excess of peracid is added in one portion the product, obtainable in high yield, is the unsaturated aldehyde-ester (393) which has also been obtained (as ethyl ester) by photochemical oxidation of the oxathian (394) followed by a reductive desulphuration. In non-polar solvents a 1 1 adduct (395) is formed between m-chloroperbenzoic acid and 3-acetoxy-3,5-dienes which is sufficiently stable (in the presence of a 17-ketone function) to be isolated and acetylated to the 6 -acetate or oxidised by chromium trioxide in pyridine to the b-ketone. ... 

Figure 4.14. Applications of oxathianes linalool [53], dimethyl acetylcitramalate [54], mevalolactone [56], malyngolide [55], and the mosquito oviposition attractant [39]. For the latter, the C-5 stereocenter was formed by a chelate-controlled reduction while the C-6 position could be produced as either epimer by a chelate or acyclic mechanism, depending on the reducing agent.

Chiral thiols 59 were derived from 10-camphorsulfonic add by reduction of the sulfony] chloride with lithium aluminum hydride, yielding a 1 4 mixture of enrfo/exo-diastereomers, which can be separated by chromatography60. Containing a hydroxy and a thiol functionality, 59 can be used for the formation of sulfur-containing heterocycles such as oxathianes which can react with carbanions (Section D.l.3.4.4.) or form enolates (Section D. 1.5.3.4.2.1.) and can direct osmium tetroxide catalyzed dihydroxylations (Section D.4.4.). 

P2i2i2j Z = 4 D = 1.46 R = 0.105 for 961 intensities (film measurements). Compound obtained by glycol cleavage of methyl 6-O-trityl-a-D-glucopyranoside, followed by reduction, sulfonylation, and ring-closure by sulfide anion. The 1,4-oxathiane ring has a distorted chair conformation, with the sulfoxide bond equatorial and the bond to the methoxyl group axial. 

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