Gassman indole synthesis indoles prepared

The Gassman indole synthesis provides a single regioisomer when ortho/para substituted anilines are employed, the yields of which are quite good generally. This provides some advantage in the preparation of 7-substituted indoles compared to other methods which normally give low yields, that is, the Fischer indole process. ... 

A total synthesis of (+)-paspalicine and (+)-paspalinine took advantage of the Gassman indole synthesis. The thiomethyl ketone was treated with A-chloroaniline (prepared by mixing aniline with t-butyl hypochlorite) to afford the azasulfonium salt, which was transformed into anilinylsulfide upon treatment with triethylamine. Desulfurization with Raney nickel was followed by the acid-catalyzed cyclization to give the hexacyclic indole intermediate. 

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. ... 

The preparation of 3-substituted oxindoles can be readily achieved by using alkylated derivatives of ethyl methylthioacetate." For example, reaction of aniline with compound 18 gave oxindole derivative 19 in 64% yield. Reduction of 19 with Raney nickel gave oxindole 20 in 70% yield, while reduction with LiAlH4 gave the corresponding indole 21 in 76% yield. The two-step route to indoles eomplements the Gassman indole synthesis. 

Many 3-substituted indoles have also been prepared with the use of a-alkyl or a-aryl-p-keto sulfides. Thus indolization of aniline 5 with 3-methylthio-2-butanone 27 furnished indolenine 28, presumably via the same mechanism discussed earlier. The indolenine 28 was relatively unstable and reduced to the indole 29 without purification. Tetrahydrocarbazole 32 was prepared in 58% overall yield. Smith et al. made excellent use of the Gassman process in the total synthesis of (-i-)-paspalicine and (+)-paspalinine. ... 

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