Chlorosulfonium salt

Gassman and co-workers developed a synthetic route from anilines to indoles and oxindoles which involves [2.3]-sigmatropic rearrangement of anilinosul-fonium ylides. These can be prepared from Ai-chloroanilines and ot-thiomcthyl-ketones or from an aniline and a chlorosulfonium salt[l]. The latter sequence is preferable for anilines with ER substituents. Rearrangement and cyclizalion occurs on treatment of the anilinosulfonium salts with EtjN. The initial cyclization product is a 3-(methylthio)indole and these can be desulfurized with Raney nickel. Use of 2-(methylthio)acetaldehyde generates 2,3-unsubstituled indoles after desulfurization[2]. Treatment of 3-methylthioindoles with tri-fiuoroacetic acid/thiosalieylie acid is a possible alternative to Raney nickel for desulfurization[3]. 

A convenient modification of the Gassman oxindole synthesis was reported using ethyl (methylsulfinyl)acetate (101) activated by oxalyl chloride to generate the same chlorosulfonium salt 102 normally generated from ethyl (methylthio)acetate 100 and elemental chlorine <96TL4631>. Thus, treatment of the sulfoxide 101 with oxalyl chloride, followed by the addition of the desired aniline, triethylamine, and finally acid cyclization of 103 affords the oxindoles 104. This procedure is particularly convenient for reactions carried out on smaller scales and for anilines that ate susceptible to electrophiUc halogenation. 

Another example that illustrates formation of a disulfonium dication as an intermediate was found in the reaction of sulfoxide 13 and thionyl chloride. Instead of the normal a-chlorosulfide Pummerer product, the reaction leads to a stable chlorosulfonium salt 66.89 Hydrolysis of the salt obtained from 2,2,8,8-tetradeuteriated sulfoxide 37 results in a 1 1 mixture of the two possible isomers, thus indicating that the chlorosulfonium salt does exist in rapid equilibrium with a symmetric S-S dication (Scheme 24). 

Oxyindoles are prepared using a modified Gassman synthesis from the chlorosulfonium salt 167 on reaction with substituted anilines <1996TL4631> (Equation 92). 

A synthetic method involving a chlorosulfonium salt (27) as intermediate, formed by treating the o -methylthiocinnamic acid (26) with sulfuryl chloride in dry chloroform, has been used to prepare a variety of benzo[6]thiophenes (28) substituted at the 2- and/or... 

Recently Wright and co-workers have described a modified Gassman oxindole synthesis. They point out the problem associated with the preparation of the chlorosulfonium salt (reagent for Method 2) from chlorine gas and ethyl methylthioacetate, and demonstrated a modified procedure that makes use of a sulfoxide as a synthetic equivalent of a sulfenyl halide48 (Scheme 11). The Gassman procedure can also be applied to AZ-alkyl anilines43. 

Dimethyi sulfoxide, when treated with a CHjClj solution of phosgene, gives the chlorosulfonium salt, [MejSClJCl, stable at temperatures below 0 C and rearranging to MeSCHjCl at higher temperatures [724],... 

Treatment of 1,3-thiazolidines (116) with chlorine affords dihydro-1,4-thiazines (117) through the ring opening of a unisolable chlorosulfonium salt (Scheme 26) <93JHC1105>. 

Generally, the reaction works well for electron-deficient anilines. A modified approach using in situ prepared chlorosulfonium salts is preferred for more electron-rich anilines. Substituted thiol derivatives can be used to produce 3-oxindoles, which can be further reduced to 3-indole derivatives that are not available via the Gassman indole synthesis. The reaction is equally useful for the preparation of isatin derivatives vide infra). Historically, the Gassman oxindole synthesis has found applications in the preparation of heterocycles with medical or insecticidal properties. The reaction also has potential applications for the synthesis of oxindole containing natural products. ... 

More recently, Wright et al. have shown that sulfoxides (11) can be converted into the desired chlorosulfonium intermediates by using oxalyl chloride. This operationally more simple approach can be used make a variety of oxindoles. Additional examples using these approaches for the in situ preparation of the chlorosulfonium salts will be shown below. 

The mechanism proposed to explain these observations shows that the oxygen of DMSO must attack the acyl carbon of oxalyl chloride in an acyl substitution reaction (Chapter 19, Section 19.2) to form an acyl-sulfonium derivative, 39. This intermediate decomposes with loss of carbon dioxide (COg) and carbon monoxide (CO) to give a chlorosulfonium salt, 40. Sulfonium salt 40 has an electrophilic sulfur that is attacked by the nucleophilic oxygen of an alcohol such as... 

One such replacement is the Swern oxidation. The oxidizing agent itself is a chlorosulfonium salt, which is generated at -78 C by the reaction of DMSO with oxalyl chloride. (Running this reaction at ambient temperature is explosive ) Slow addition of the alcohol at low temperature, followed by the addition of a tertiary amine such as triethyl amine (EtjN), yields the product. 

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