Sulfoxides alkoxysulfonium salts

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). 

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). 

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. 

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. 

Johnson, C. R., Bacon, C. C., Kingsbury, W. D. Chemistry of sulfoxides and related compounds. XXXVIII. Oxidation of sulfides with 1-chlorobenzotriazole. Preparation of amino- and alkoxysulfonium salts. Tetrahedron Lett. 1972, 501-503. 

Alkoxysulfonium salts. Methyl chlorosulfinate and dimethyl sulfoxide form the adduct (a), isolated as the salt (1). This product (1) reacts with various... 

The reaction of dimethyl sulfoxide, oxalyl chloride and an alcohol is normally carried out at -78 or —60 °C, since the formation of the alkoxysulfonium salt 29 is rapid at this low temperature. After addition of the base triethylamine, the mixture may be warmed to —30 °C or higher to promote proton abstraction and fragmentation. The use of diisopropylethylamine instead of triethylamine as the base or addition of pH 7 phosphate buffer can, in the rare cases when it does occur, reduce the extent of enoUzation and therefore minimize any racemization or rearrangement of p,7-double bonds. 

The original Pfittner-Moffatt procedure for alcohol oxidation by activated dimethyl sulfoxide utilized dicyclohexylcarbodiimide (DCC) and a source of protons such as polyphosphoric acid or pyridinium tri-fluoroacetate. The use of strong acids such as the common mineral acids must be avoided since, although acidic conditions are initially required, the reaction must readily become basic in the later stages of the process. Mechanistically it is reasonable to suggest that the activation follows the pattern whereby initial attack of the nucleophilic sulfinyl oxygen of dimethyl sulfoxide, with the protonated carbodiimide, forms a sulfonium isourea. This is followed by displacement of dicyclohexylurea by the alcohol to form an alkoxysulfonium salt. Base treatment of this salt forms an ylide, which collapses via the proven cyclic mechanism to the carbonyl compound and dimethyl sulfide (Scheme 4). 

Alkoxysulfonium salts are cleaved by bromide and iodide ions (145) to sulfoxides with retained configurations indicating a Sn2(C) displacement at alkoxy carbon by the soft nucleophiles. The use of equimolar chloride ion leads to a mixture of sulfides and partially racemized sulfoxides. The intervention of sulfurane intermediates has been postulated (146, 147) for the reaction. 

Fluoride ion causes racemization and inversion of sulfoxide configurations. Hydroxide ion displaces the alkoxy group from alkoxysulfonium salts resulting in net inversion at sulfur (148). 

Sodium hydroxide Sulfoxides from alkoxysulfonium salts s. 27,126 reactions of optically active alkoxysulfonium salts s. M. Moriyama et al., Chem. Ind. 1976, 163 NaOH >st -> >so OR... 

Alkoxysulfonium salts Sulfenic acid esters Sulfoxides Sulfoxonium salts... 

Mild oxidation of primary and secondary alcohols, promoted by oxalyl chloride activation of dimethyl sulfoxide, evidently involving the dimethyl alkoxysulfonium salts. Upon the addition of base, the intermediates rearrange intramolecularly to generate aldehydes or ketones, respectively ... 

The reduction of alkoxysulfonium salts (formed by alkylation of sulfoxides with methyl fluorosulfonate) with sodium cyanohydridoborate in dichloromethane is catalyzed by 18-crown-6 [32] (see Eq. 13.24). By this method, dibutyl, diphenyl, dibenzyl, and tetramethylene sulfoxides are reduced to the corresponding sulfides in 85%, 77%, 91%, and 87% yields, respectively. 

A soln. of cw-9,10-epoxystearic acid in benzene added dropwise with stirring during 10 min. to a soln. of 2,4,6-trinitrobenzenesulfonic acid in anhydrous dimethyl sulfoxide, stirring continued 15 min., stirred into excess cold ether-ethyl acetate (2 1), the solvent layer decanted, and the oily lower layer stirred 12-14 hrs. with water /hreo-9,10-dihydroxystearic acid. Y 65-70%. Also erythro- from trans-isomer, and prepn. of f. l-hydroxy-2-(alkoxysulfonium) salts, s. M. A. Khud-dus and D. Swern, Tetrah. Let. 1971, 411. 

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