Sulfoxides by oxidation of sulfides

Preparation of various enantiomerically pure sulfoxides by oxidation of sulfides seems feasible in the cases where asymmetric synthesis occurs with ee s in the range of 90% giving crystalline products which can usually be recrystallized up to 100% ee. Aryl methyl sulfides usually give excellent enantioselectivity during oxidation and are good candidates for the present procedure. For example, we have shown on a 10-mmol scale that optically pure (S)-(-)-methyl phenyl sulfoxide [a]p -146 (acetone, o 1) could be obtained in 76% yield after oxidation with cumene hydroperoxide followed by flash chromatographic purification on silica gel and recrystallizations at low temperature in a mixed solvent (ether-pentane). Similarly (S)-(-)-methyl o-methoxyphenyl sulfoxide, [a]p -339 (acetone, o 1.5 100% ee measured by HPLC), was obtained in 80% yield by recrystallizations from hexane. 

Oxidation of sulfides. The synthesis of chiral sulfoxides by oxidation of sulfides has... 

Sulfoxides are easily obtained by oxidation of sulfides. They can be further oxidized to sulfones. Many reagents have been used, and the possibility to synthesize selectively sulfoxides and sulfones, often in the presence of other sensitive functionalities, is an important feature for synthetic applications. The reaction is well documented [75], and only a few notable aspects are mentioned here. 

With peroxides and peroxycarboxylic acids the oxidation of sulfides to sulfoxides proceeds much more rapidly than that of sulfoxides to sulfones. The oxidation occurs by electrophilic attack of the peroxide on sulfur and, as the nucleophilicity of the sulfur atom is reduced in the sulfoxide compared to that of the sulfide, the sulfoxides are normally easily isolable (generally 1 mol of oxidant is used). Over-oxidation of sulfoxides can also be avoided with specific reagents sodium metaperiodate has been usually used. Sulfoxides are also obtained exclusively by oxidation of sulfides with the couple Mn02/Me3SiCl in methanol [76]. 

Sulfoxides,5 Oxidation of sulfides to sulfoxides can be effected with CAN (2 equiv.) in CH2C12/H20 catalyzed by Bu4NBr at 25° (90-100% yields). A Pummerer-type rearrangement does not occur under these conditions. 

Finally, zearalenone was obtained by intramolecular alkylation of the carbanion a to the benzylic sulfide, which occurs readily with potassium hexamethyldisilazane. After cyclization, the double bond was created by oxidation of sulfide to sulfoxide followed by pyrolytic elimination, a technique described in more detail in the next section (Scheme 12). 

The biscinchona alkaloid ligands can also be used for the asymmetric oxidation of sulfides to sulfoxides with hydrogen peroxide as the oxidant in the presence of tungsten(VI) oxide, or layered double hydroxide (LDH) supported 0s04 as catalyst (Scheme 3.46) [375, 376]. The approach can also be used to affect a kinetic resolution of racemic sulfoxides by oxidation of one enantiomer to the sulfone (Scheme 3.47) [376]. 

Sulfoxides with a -hydrogen atom readily undergo syn elimination on pyrolysis to form alkenes. These reactions take place by way of a concerted cyclic pathway and are therefore highly stereoselective. The sulfoxide anti-24, for example, gives predominantly trans-methylstilbene, whereas the corresponding 5yn-isomer gives mainly cis-methylstilbene (2.22). Because sulfoxides are readily obtained by oxidation of sulfides, the reaction provides another useful method for making carbon-carbon double bonds. 

Various halogenating agents in the presence of a chiral additive have been used as oxidant systems to prepare sulfoxides (usually in low ee). Thus, the combinations iodine/water/(+)-2-methyl-2-phenylsuccinic acid [80] or N-chloroamides/chiral alcohols [81-83] gave sulfoxides with -10% ee at best. Menthyloxysulfonium salts are prepared by oxidation of sulfides in presence of menthol. They can be isolated and recrystallized, with improvement of the diastereoisomeric excess. They are interesting intermediates for the synthesis of chiral sulfoxides, which are obtained by aqueous basic hydrolysis, with inversion of configuration at sulfur. Sulfoxide may also be obtained (in lower ee) by a one-pot reaction, without isolation of the sulfonium salt. Thus, 1-chlorobenzotriazole in the presence of (-)-menthol in methylenechloride oxidizes benzyl p-tolyl sulfide into the sulfonium salt (42a) (Figure 1.3). After crystallization and hydrolysis, (-)-benzyl p-tolyl sulfoxide is afforded in 87% ee [84]. A chiral derivative of N-chlorocaprolactam has been used to prepare some sulfoxides in low ee [85]. 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Sulfinic esters, aromatic, by oxidation of disulfides in alcohols, 46, 64 Sulfonation ot d,l camphor to d,l-10-camphorsulfomc acid, 45,12 Sulfoxides, table of examples of preparation from sulfides with sodium metapenodate, 46,79 Sulfur dioxide, reaction with styrene phosphorus pentachlonde to give styrylphosphomc diclilonde, 46,... 

The earliest attempts to obtain optically active sulfoxides by the oxidation of sulfides using oxidants such as chiral peracids did not fare well. The enantiomeric purities obtained were very low. Biological oxidants offered great improvement in a few cases, but not in others. Lately, some very encouraging progress has been made using chiral oxaziridines and peroxometal complexes as oxidants. Newer developments in the use of both chemical oxidants and biological oxidants are described below. 

A number of studies describing the oxidation of sulfides to sulfoxides by biological oxidizing agents have been published over the years2 9,13,107- Microbial systems are often... 

The various oxidation states of sulfur have been determined by polarography. The electrochemical oxidation of sulfide ions in aqueous solution may lead to the production of elementary sulfur, polysulfides, sulfate, dithionate, and thiosulfate, depending on the experimental conditions. Disulfides, sulfoxides, and sulfones are typical polarographically active organic compounds. It is also found that thiols (mer-captans), thioureas, and thiobarbiturates facilitate oxidation of Hg resulting thus in anodic waves. 

Table 11 Result of one-pot preparation method of optically active sulfoxides (64a-d) by a combination of oxidation of sulfide and enantiomeric ...

Rj = PhCH2 R2 = Ph Rj = Ph, n-C12ttz R2 = Me Scheme 6.34 Oxidation of sulfides to sulfoxides and sulfones by silica-supported sodium periodate. 

Scheme 6.35 Oxidation of sulfides to sulfoxides by alumina-supported iodobenzene diacetate.

Nitrogen dioxide (NO ) reacts with a wide variety of functional groups and it is the reagent of choice for a number of synthetic transformations. For example, the selective oxidation of sulfide to sulfoxide by NO forms the basis for the commercial production of dimethyl sulfoxide (from dimethyl sulfide) via a catalytic procedure (see below).250 Some representative examples of oxidative transformations carried out with NO are presented in Chart 8. 

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