Indole derivatives thallation

Thallation of benzanilides with thallium tris(trifluoroacetate) in a mixture of trifluoroacetic acid and ether gave the c rr/to-thallated products. Reaction of these products with copper(I) acetylide in acetonitrile led to the 2-benzamidotolanes (119), which were eventually elaborated into the 2-phenyl-indole derivatives. 111 ... 

Preparation of bromoindoles by replacement of metallic substituents have included oxidation of indolylmagnesium bromide by p-nitrobenzoic acid to give 3-bromoindole (67BSF1294), thallation procedures (illustrated in Scheme 18 also applied to the synthesis of chloroindoles) [85H(23)3113 86H(24)3065 87CPB3146, 87H(26)2817 89H(29)1163], and the use of lithium derivatives. The thallation reactions provide access particularly to 4- and 7-bromoindoles. Quenching the protected 2-lithium derivative of indole with 1,2-dibromotetrachloroethane gave an 87% yield of 2-bromoindole (92JOC2495). 

Thallation of l-methoxyindole-3-carbaldehyde with thallium trisfluo-roacetate followed by treatment with potassium iodide gave the 4-iodo derivative in 91% yield, and this has been converted into many other 1-methoxyindole derivatives (86CPB677). When the thallated indole reacted with methyl acrylate in the presence of a catalytic quantity of pal-ladium(ll) acetate, 47% of the product was the 4-derivative 160, but 11% of the 5-isomer was also formed (86CPB4116). 

Indolines are useful intermediates for the synthesis of indoles with substituents in the carbocyclic ring. In electrophilic substitutions, they behave like anilines the example shows iV-acetylindoline undergoing regioselective 7-thallation. Nitration of indoline 2-carboxylic acid gives the 6-nitro-derivative separation... 

Thallation of 3-acyl indoles gives the 4-thallated products, which can be converted to both the 4-nitro and 4-azido derivatives in copper(II)-promoted processes <89H(29)643>. The nitro compound is formed by heating the organothallium intermediate with sodium nitrite and copper sulfate in DMF at 100°C. This methodology has been used in a total synthesis of indolactam-V <90T6623>. 

Synthesis of indoles via 2,3-dihydroindoles (indolines) is sometimes done in order to achieve a specific substitution pattern in the carbocyclic ring <67RCR753>. Indolines, being aniline derivatives, readily undergo electrophilic substitution at C5. Indolines can also be used to achieve selective 7-substitution. The 1-Boc derivative of indoline can be lithiated at C7 <92H(34)i03i> and 1-acetyl-indoline is thallated at C7 <89H(29)643>. These organometallic intermediates can be functionalized and then aromatized to indoles. There are a number of methods which have been developed for oxidative aromatization of dihydroindoles. Table 3 cites some examples. 

Regioselective thallation (see Section 2.03.4.2) can be used to introduce halogen at C4 or C7 of the indole ring. For example, 5,7 and 6,7-dibromoindole-3-carboxaldehyde can be converted to the corresponding 4-bromo derivative by reaction with T1(02CCF3)3 and CuBrj <89H(29)1663>. 

Indole-5-boronic add has also been used successfully in Suzuki coupling <92H(34)1395). Organothallium derivatives have also been used in Suzuki coupling reactions. The 4-substituted thallation intermediate from indole-3-carboxaldehyde can be coupled with both aryl and vinyl-boronic acids (Equation (122)) <86CPB397i>. 

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