Chemoselective reactions sulfide

The oxidation of sulfides to sulfoxides (1 eq. of oxidant) and sulfones (2 eq. of oxidant) is possible in the absence of a catalyst by employing the perhydrate prepared from hexafluoroacetone or 2-hydroperoxy-l,l,l-trifluoropropan-2-ol as reported by Ganeshpure and Adam (Scheme 99 f°. The reaction is highly chemoselective and sulfoxidation occurs in the presence of double bonds and amine functions, which were not oxidized. With one equivalent of the a-hydroxyhydroperoxide, diphenyl sulfide was selectively transformed to the sulfoxide in quantitative yield and with two equivalents of oxidant the corresponding sulfone was quantitatively obtained. 2-Hydroperoxy-l,l,l-fluoropropan-2-ol as an electrophilic oxidant oxidizes thianthrene-5-oxide almost exclusively to the corresponding cw-disulfoxide, although low conversions were observed (15%) (Scheme 99). Deprotonation of this oxidant with sodium carbonate in methanol leads to a peroxo anion, which is a nucleophilic oxidant and oxidizes thianthrene-5-oxide preferentially to the sulfone. 

In 2002, Ichihara and coworkers reported on the utilization of a Keggin-type phos-phomolybdate (NH4)3PMoi2O40 on apatite as catalyst for the solvent-free epoxidation of olefins (see Section III.A.3.c) and the oxidation of sulfldes and sulfoxides in the presence of urea hydrogen peroxide (Scheme 104) . Chemoselectivities of the oxidation of the sulfides were good [product ratios (sulflde/sulfoxide) 84/16 up to 91/9] depending on the substrate, temperature and reaction time. 

Although periodates also oxidize polycyclic aromatic hydrocarbons, phenols, hydrazines, active methylene compounds and sulfides, chemoselectivity can usually be achieved and glycol cleavage oxidation takes precedence. For example, the diol moiety in the diethyl dithioacetal derivative of o-glucose can be selectively oxidized in good yield (equation 6). In contrast, LTA is less selective dum periodate and oxidizes a far greater variety of oiganic compounds. Consequently, in order to minimize undesired reactions, it is customary to add LTA slowly to avoid contact of die initially formed products widi an excess of the oxidant (equation 7). ... 

Sodium metiq>eriodate, NaI04, is a two-electron chemoselective oxidant and when absorbed on alumina oxidizes alcohols to carbonyl compounds and sulfides to sulfoxides without overoxidation to sul-fones. 2 Alkenic double bonds in the substrate remain intact during this oxidation. Typically reactions are performed in 95% ethanol at room temperature for a few hours and with good (85-90%) yields. 

Many other examples of chemoselective enone reduction in the presence of other reducible functionalities have been reported. For instance, the C—S bonds of many sulfides and thioketals are readily cleaved by dissolving metals. " Yet, there are examples of conjugate reduction of enones in the presence of a thioalkyl ether group." " Selective enone reduction in the presence of a reducible nitrile group was illustrated with another steroidal enone. While carboxylic acids, because of salt formation, are not reduced by dissolving metals, esters" and amides are easily reduced to saturated alcohols and aldehydes or alcohols, respectively. However, metal-ammonia reduction of enones is faster than that of either esters or amides. This allows selective enone reduction in the presence of esters"" and amides - -" using short reaction times and limited amounts of lithium in ammonia. 

The lower reactivity of Raney Ni towards sulfones allows the chemoselective desulfurization of (4) with Raney W-2, but an appreciable amount of reduction of keto groups was observed. Raney Ni W-2 also tolerates sulfonamides in this work an ionic mechanism was suggested in order to explain the substitution reaction observed. Lactones,keto lactones," and unsaturated lactoneswere tolerated during the desulfurization of sulfide or dithioketal" groups, but deactivated (e.g. by acetone) Raney Ni was generally used. In contrast, carbon-halide bonds are cleaved where the desulfurization is stereoselective only because the product is the thermodynamically more stable d5-lactone (equation 2)." e-" f... 

Electrolytic desulfurization of o-aminobenzyl sulfide, sulfoxide or sulfone illustrates carbon-sulfur bond cleavage. Careful control of the reaction conditions is important to achieve chemoselectivity (Scheme 17). Trifluoromethyl substituents are not reduced under the conditions used (Cd sheet ca-... 

The reaction between sulfur ylides and carbonyl compounds entails attack of the ylide on the carbonyl to form a betaine, which then collapses with expulsion of the neutral sulfide or sulfoxide (Scheme 1 X = R2S ). - - a theoretical study of this mechrmism has appeared. Ylides belonging to the general classes of (1) and (2) differ in stability and in the relative rates of the two mechanistic steps. Specifically, the more stable (2) reacts reversibly with carbonyl groups, whereas (1) undergoes a kinetic addition to the substrate followed by a rapid collapse of the betaine to an epoxide. Differences in chemoselectivity and stereoselectivity between Ae ylides are attributed to this key difference. - - ... 

Examples are known (22-25) of the oxidation of macromolecular substrates containing sulfide functional groups, with chiral polysulfoxides being prepared by different synthetic approaches ( 6,27.). However, the asymmetric oxidation of polymeric precursors was only performed with very limited degrees of chemoselectivity and enantioselectivity (27). The asymmetric oxidation reaction employed in this work is accomplished with a moderate enantioselectivity, which is nevertheless on the order of magnitude as those obtained with low molecular weight substrates (11.28.29). 

The oxidation of sulfides to sulfoxides has been widely explored with many different oxidizing reagents very few of these reagents however, have general application. Many are too reactive, overoxidizing sulfoxides to sulfones, particularly when the reagent is in excess. With other reagents, careful control of the reaction parameters is necessary or the chemoselectivity suffers. 

We shall be using [2,3] sigmatropic shifts in the reactions of allylic alcohols so this section is an introduction to that as well as describing perhaps the most tightly controlled method for making allylic alcohols. Allylic sulfides 40 are easily oxidised chemoselectively with reagents such as sodium periodate to the corresponding sulfoxides 41. More powerful oxidants tend to form the sulfone 42. 

---