Alkoxysulfonium salts

Methoxydimethylsulfonium and Trimethylsulfoxonium Salts. Alkylating agents react with DMSO at the oxygen. For example, methyl iodide gives methoxydimethylsulfonium iodide (10) as the initial product. The alkoxysulfonium salts are quite reactive and, upon continued heating, either decompose to give carbonyl compounds or rearrange to the more stable trimethylsulfoxonium salts, eg, (11) (eq. 21) (52) ... 

Dupont Durst et al. (1974) have used 18-crown-6 to solubilize NaBH3CN in a methanol/dichloromethane mixture, the solution reducing alkoxysulfonium salts to the corresponding sulfides in high yields. 

Johnson and McCants (161) were the first to show that the alkaline hydrolysis of alkoxysulfonium salts, obtained by 0-alkylation of sulfoxides, proceeds with inversion of configuration at sulfur. This method was employed to interconvert (/ )- and (5)-benzyl p-tolyl sulfoxides 37 as shown in Scheme 21. In contrast to the hydroxide anion, the chloride, bromide, and iodide anions as well as the nitrogen atom of pyridine react with chiral ethoxydiarylsulfonium salts, not at sulfur but at the a-carbon atom of the ethoxy group, yielding the starting sulfoxide with retained configuration (284). On the other hand, the nucleophilic attack of the fluoride anion is directed at sulfur as in the case of the hydroxide anion (285). 

The original observation of Johnson that alkaline hydrolysis of alkoxysulfonium salts takes place with inversion of configuration at sulfur was utilized recently (110) to invert the configuration of sulflnamides. As was already mentioned, (+)-(5)-p-toluenesulflnyl-pyrrolidine 120 was treated with methyl triflate to give the corresponding methoxypyrrolidino-p-tolylsulfonium triflate 119. The crude salt 119 was then subjected to mild alkaline hydrolysis and gave the enantiomeric sulflnamide (-)-reaction sequence takes place with at least 91% inversion. 

The isolation and stereochemical studies of a cyclic alkoxysulfonium salt (48) have been reported." Such a species has previously been proposed as an intermediate in the hydrolysis of the chlorosulfurane (49). 

Sulfonium salts of thiepanes are readily formed by electrophilic attack of alkyl halides on the cyclic thioether. Thus, thiepane (35) was found to yield a sulfonium iodide (123), which at elevated temperatures and in the presence of excess methyl iodide underwent ring cleavage to yield 1,6-diiodohexane (isolated as the 1,6-diphenoxy derivative Scheme 24) (53M1206). The alkoxysulfonium salt (124) formed by reaction of (35) with t-butyl hypochlorite (equation 23) was characterized as a stable hexachloroantimonate (67JOC2014). Reduction of thiepane 1-oxide (115) to thiepane has been achieved using an aqueous solution of NaHSC>3 (72JOC919). A hydroxysulfonium salt intermediate (125) has been proposed in the latter reduction reaction which provides a general method for sulfoxide reductions under mild conditions (equation 24). 

The mechanism of the Parikh-Doering oxidation involves formation of O-di-methylsulfoxonium sulfate from the reaction of DMSO with S03. Displacement on the sulfur by the alcohol gives the alkoxysulfonium salt intermediate, which undergoes base-catalyzed elimination to afford the dimethyl sulfide and the aldehyde. This reaction must be carried out so the hydrogen sulfate of the alcohol is not formed first, otherwise no oxidation would occur. 1143 44 ... 

Sometimes, when intramolecular processes are favoured, the intermediate alkoxysulfonium salt suffers displacement from a nucleophile, instead of the expected evolution to an aldehyde or ketone.53... 

Procedure A DMSO and TFAA are reacted at -78 to -60°C for ca. 10 min producing 22, which is reacted with the alcohol at —78 to -60°C for ca. 30 min. The amine is added to the resulting solution of alkoxysulfonium salt 24 and the resulting mixture is left to reach slowly at room temperature. Procedure C like Procedure A but the solution of the alkoxysulfonium salt 24 is left to reach at room temperature before the amine is added. 

Quite remarkably, although TFAA-activated DMSO is decomposed above —30°C, there is one published report of successful oxidation, in which TFAA is added over a solution of DMSO and the alcohol, kept at —20°C.125 This oxidation succeeds apparently, because at this temperature, TFAA-activated DMSO suffers decomposition slower than conversion into an alkoxysulfonium salt by attack of the alcohol. 

The differential stability of alkoxysulfonium salts, derived from diverse alcohols, and the lesser tendency of hindered alcohols to provide trifluor-oacetate side compounds can explain some interesting selective oxidations reported in the literature.125,130... 

A large number of other materials have been used to activate dimethyl sulfoxide for the oxidation of primary and secondary alcohols and new methods are still being introduced. The vast majority of these reactions proceed via an alkoxysulfonium salt and consequently are variants of the original Pfitzner-Moffatt procedure. Very few of tiiese methods have been exhaustively tested and their advantages are often not apparent. 

One potential activator for dimethyl sulfoxide that in practice turns out to be very poor, is phosgene. However, a related oxidation of alcohols using dimethyl sulfoxide does use phosgene for the preparation of a chloroformate (or carbonochloridate) such as (29). - This reacts with dimethyl sulfoxide to give, after spontaneous loss of carbon dioxide, an alkoxysulfonium salt (30) which upon treatment with tri-ethylamine fonns the carbonyl compound (Scheme 7). Relatively little use appears to have been made of this method. 

Alkylation may take place either on sulfur or on oxygen to form either oxosulfonium or alkoxysulfonium salts. Whereas the former are useful in carbanion chemistry, the latter can be used in oxidizing reactions. If trimethylsulfoxonium iodide is heated with a mild base in deuterium oxide, the hydrogen atoms in the salt are replaced by deuterium. 

In its simplest application as an oxidizing agent, dimethyl sulfoxide displaces a reactive alkyl halide or sulfonate to give an alkoxysulfonium salt (Scheme 2.28a). This collapses in the presence of a mild base with the elimination of dimethyl sulfide and the formation of a new ketone or aldehyde. 

Another method of aetivation is known as the Swern oxidation. Under these conditions a reactive dimethylchlorosulfonium chloride is formed from the reaction of dimethyl sulfoxide and oxalyl chloride (Scheme 2.28b). This then reacts with an alcohol to give an alkoxysulfonium salt. In the presence of a base (triethylamine) this salt fragments with the formation of a carbonyl compound (Scheme 2.28c). 

Reaction with epoxides. Dimethyl sulfoxide and a strong acid (2,4,6-trinitro-bcnzcncsulfonic acid, TNBSA, was used) reacts with epoxides (1) to form alkoxy-sulfonium salts (2) in good yield. Since hydrolysis of alkoxysulfonium salts proceeds exclusively by attack at sulfur, the reaction provides a stereospecific synthesis of 1,2-glycols. Thus the reaction of lis- and rrans-9,10-epoxystearic acids with DMSO-... 

It is shown [79] that compounds VIII-X are oxidized much more easily in the presence of trace amounts of bromide ions when compared with their corresponding exo isomers, with X = COJ, CH2OH, CMe20H, Y = H. Controlled-potential electrolyses of VIII-X yield mixtures of diastereomeric sulfoxides (for VIII) or of diastereomeric alkoxysulfonium salts (for IX and X). These results are explained in terms of a neighboring carboxylate or alcohol participation in the bromide mediated oxidation of the thioethers. 

The first step of the mechanism of the Corey-Kim oxidation is the reaction of dimethylsulfide with A/-chlorosuccinimide to generate the electrophilic active species, S,S-dimethylsuccinimidosulfonium chloride Corey-Kim reagent) via dimethylsulfonium chloride. The sulfonium salt is then attacked by the nucleophilic alcohol to afford an alkoxysulfonium salt. This alkoxysulfonium salt is deprotonated by triethylamine and the desired carbonyl compound is formed. The dimethylsulfide is regenerated, and it is easily removed from the reaction mixture in vacuo. In the odorless Corey-Kim oxidation instead of dimethylsulfide, dodecylmethylsulfide is used. This sulfide lacks the unpleasant odor of DMS due to its low volatility. 

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