Sulfenes as intermediates

Oxathiene dioxides from sulfonic acid chlorides Sulfene as intermediate... 

Gilbert and coworkers18 were able to detect ESR spectra of sulfinyl radicals together with other sulfur-centered radicals during the oxidation of disulfides and thiols with a titanium(III)-peroxide couple reaction mechanisms involving sulfenic acids as intermediates have been discussed. 

We mentioned earlier in this section that when a sulfonyl group possesses a hydrogen on the carbon adjacent to the S02 group, an elimination-addition mechanism (193)—(194) for substitution, involving a sulfene as an intermediate, can be in competition with the direct substitution pathway and may, in fact, be preferred. Let us now discuss what is known about the mechanistic details of substitutions going by such an elimination-addition (sulfene) pathway, and the factors determining how readily such a process will occur under different conditions. 

As a consequence of the conformational mobility of the thiepane 1-oxide ring (115) it was possible to form the necessary planar five-membered cyclic transition state for a thermal E elimination reaction (equation 19). The acyclic sulfenic acid intermediate was not isolated but rearranged to c/s-2-methylthiane 1-oxide by an intramolecular cyclization mechanism (75TL2235). 

A study of the solvent effects on the rate of thermal racemization of chiral allyl sulfoxides has revealed that polar solvents significantly decelerate the racemization [108], The reaction proceeds by way of a reversible and concerted rearrangement achiral allyl sulfenates are formed as intermediates and an intramolecular a, 7-shift of the allyl group between the sulfoxide oxygen and sulfur termini occurs as shown in Eq. (5-38). 

Triphenyl-l, 3-thiaphosphetane 1,1-dioxides, for example, 521, are suggested as intermediates in the reaction of sulfenes (from dehydrohalogenation of methanesulfonyl halides) with triphenylphosphine ylides. °... 

The oxidation of thiols follows a completely different course as compared with the oxidation of alcohols, because the capacity of the sulfur atom to form hypervalent compounds allows it to become the site of oxidation. Thiols are readily oxidised to disulfides by mild oxidants such as atmospheric oxygen, halogens or iron(III) salts (Scheme 6). This type of reaction is unique to thiols and is not undergone by alcohols, it is a consequence of the lower bond strength of the S-H as compared with the O-H bond, so that thiols are oxidised at the weaker S-H bonds, whereas alcohols are preferentially oxidised at the weaker C-H bonds (Scheme 7). The mechanism of oxidation of thiols may be either radical or polar or both (Scheme 6). The polar mechanism probably involves transient sulfenic acid intermediates like (7) and (8). In contrast, thiols react with more powerful oxidants, like potassium permanganate, concentrated nitric acid or hydrogen peroxide, to yield the corresponding sulfonic acids (10). This oxidation probably proceeds via the relatively unstable sulfenic (7) and sulfinic acids (9), which are too susceptible to further oxidation to be isolated (Scheme 8). 

Sulfenes are very reactive and occur as intermediates in several synthetically important reactions (see p. 115).3b They have not been isolated and are formed by base-induced eliminations for instance, a sulfene is formed in the reaction of a sulfonyl chloride containing at least one a-hydrogen atom with a tertiary amine. As an illustration, when phenylmethanesulfonyl chloride (97) is treated with pyridine, phenylsulfene (98) is formed as a transient species (Scheme 65). 

When a nitrile bearing an a-hydrogen such as a-sodiobenzyl cyanide reacts, an acyclic product, 2,3,4-triphenyl-2-butenenitrile, is obtained through rearrangement of a sulfenic acid intermediate to an alkene with extrusion of SO (Scheme 11). 

Further insight was obtained by kinetic studies, which showed that reaction of methanesulfonyl chloride with triethylamine and 2-propanol to form isopropyl methane-sulfonate was first order in sulfonyl chloride, first order in triethylamine and zero order in 2-propanol42. This observation requires the formulation of an intermediate which is formed in the rate-determining step and then reacts with the zero-order reagent in a relatively fast step. The kinetic observation gives strong support for the idea of the sulfene as an intermediate in these reactions. 

Setting of wool and hair by either steam or hot alkaline solutions is a very old technique [54]. Steam is also very effective for producing a permanent set. Alkali and steam are known to cleave the disulfide bond in keratins [55-57] and alkaline treatments are reputed to be the most effective hair-straightening compositions because they provide the most permanent set (see the section on hair straightening in this chapter). The reaction with hydroxide is summarized by Equation E. Because sulfenic acids are generally unstable species [58], they have been suggested as intermediates that can react with the nucleophilic side chains in the keratin macromolecules [56]. 

This reaction mechanism has yet to be confirmed. Indeed, the second reaction product shown in the reaction (1). i.e., sulfenic acid RSOH, has never been detected experimentally [15]. This is not surprising since most such species are known to be unstable. However, sulfenic acids, formed as intermediates were suggested to be a source of sulfinyl radicals during the course of hydroxyl radical-induced oxidation of thiols and disulfides [16]. 

Penicillin sulfoxides can be epimerized by heat to afford thermal equilibrium mixtures of a- and /3-sulfoxides, the position of the equilibrium depending on the C(6) side chain (Scheme 5). Deuterium incorporation studies support a sulfenic acid, e.g. (18), as the intermediate in these transformations. This mechanism is also supported by the finding that when an a-sulfoxide epimerizes to a /3-sulfoxide there is a simultaneous epimerization at C(2) (71JCS(C)3540). With irradiation by UV light it is possible to convert a more thermodynamically stable /3-sulfoxide to the a-sulfoxide (69JA1530). 

On the basis of these findings, the reaction of acyl imines with methanesulfony 1 chloride-triethylamine is not expected to proceed via a sulfene intermediate as previously proposed [99]. Again, a carbanion intermediate accounts nicely for the experimental facts. The electrophihcity of the hetero-l,3-diene is exdemely high, therefore the carbanion, formed on reaction of triethylamme with methanesulfonyl chloride, should undergo nucleophilic attack at C-4 of the hetero-1,3-diene faster than sulfene formabon by chloride elimination. 

The reaction of enamines with ketene (146) and sulfene (147) are presumed to proceed by a two-step process involving an iminium intermediate such as 99. In fact, reaction with all electrophilic olefins such as acrylonitrile and related reagents could be thought of as going through an iminium intermediate similar to 99. Another example is given by addition to an enamine... 

However, alcohol-free solutions of diazomethane146 must be used to avoid destruction of the intermediate sulfene and a stronger base such as 1,5-diazabicyclo [4.3.0] non-5-ene is required for the final dehydrohalogenation step to obtain sulfones 19a,d. 

The photolysis of various substituted thiete dioxides under similar conditions resulted in the formation of the unsaturated ketones (255)264, most probably via a vinyl sulfene intermediate followed by a loss of sulfur monoxide as shown in equation 96. The same results were obtained in the thermolysis of 6e (R1 = R3 = Ph R2 = R4 = H)231, which further demonstrates that similar mechanisms are operative in thermolyses and pho-tolyses of thietane dioxides and thiete dioxides. 

---