Reactions of indoles

The classic addition of C3 tethered amine derivatives onto C2 of indolium ions has been used to access hexahydropyrrolo[2,3-fc]indole frameworks 060L4303, 060F6011 . An alternative and unique strategy for accessing similar pyrrolo[2,3-fc]indole polycyclics 137 has 

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Epoxides and aziridines are also capable of electrophilic subsitution of indoles. Indolylmagncsium bromide and cyclohexene oxide react to give 3-(lrans-2-hydroxycyclohexyl)indole[14]. Reaction of indoles with epoxides also occurs in the presence of Lewis acids. For example, indole reacts with methyl 2S,3R-epoxybutanoate at C3 with inversion of configuration[15]. 

Lewis acids such as zinc triflate[16] and BF3[17] have been used to effect the reaction of indole with jV-proiected aziridine-2-carboxylate esters. These alkylations by aziridines constitute a potential method for the enantioselective introduction of tryptophan side-chains in a single step. (See Chapter 13 for other methods of synthesis of tryptophans.)... 

Alkylation can also be accomplished with electrophilic alkenes. There is a dichotomy between basic and acidic conditions. Under basic conditions, where the indole anion is the reactive nucleophile, A-alkylation occurs. Under acidic conditions C-alkylation is observed. The reaction of indole with 4-vinylpyri-dine is an interesting illustration. Good yields of the 3-alkylation product are obtained in refluxing acetic acid[18] whereas if the reaction is done in ethanol containing sodium ethoxide 1-alkylation occurs[19]. Table 11.2 gives some examples of 3-alkylation using electrophilic alkenes. 

The conversion of indoles to oxindoles can be achieved in several ways. Reaction of indoles with a halogenaling agent such as NCS, NBS or pyridin-ium bromide perbromide in hydroxylic solvents leads to oxindoles[l]. The reaction proceeds by nucleophilic addition to a 3-haloindolenium intermediate. 

Reaction of indole with excess of methyl iodide at 110°C gives a tetramethyl derivative (66). The intermediate 2,3-dimethylindole (65) is thought to arise by rearrangement of the 3,3-dimethyl-3Ff-indolium cation (64). 

Thermal isomerization and decomposition reaction of indole behind reflected shoek waves at 1050-1650 K have been explained by a preequilibrium between 17/-indole and 3//-indole (97JPC(A)7787). 

New reactions of indole nucleus and their synthetic applications 99YZ35. 

Coupling reactions of indole-3-acetic acid derivatives have also p ovided convenient routes to indolo[2,3-a]carbazoles (Scheme 5). An iodine-p-omoted coupling... 

The formation of the tetiamethyl derivative 138 has been suggested from the reaction of indole and acetone using maleic acid as catalyst (61JOC4263). However,... 

Genkina et al. (1979, 1981, 1985) investigated azo coupling reactions of indoles with fused benzo and benzothiopheno rings, namely 4,5- and 6,7-benzindole, 4,5,6,7-dibenzindole (12.42), indolo[6,5]-, -[4,5]-, and -[5,4]-benzo[Z ]thiophene (12.43 to 12.45). Arenediazonium ions reacted with all these indole derivatives at the 3-position. 

Table 4.13 Photoinduced Diels-Alder reactions of indoles 64 and dienes 61-63 with sensitizers 59 and 65...

The theory of the mechanistic spectrum generally snggests that photochemical reactions between donors and acceptors in the delocalization band could be similar to thermal reactions between strong donors and acceptors in the pseudoexcitation band. This is fnrther snpported by the reactions of indoles with electron-accepting... 

A photochemical reaction of indole with acrylonitrile gave an a-cyanoethylated indole (delocalization band in Scheme 10) [46]. This is a photochemical reaction in the delocalization band. 

Scheme 10 Mechanistic spectrum of the reactions of indoles with unsaturated acceptors...

Instead of Bronsted acids, lanthanide triflates can be used to catalyze the reaction of indole with benzaldehyde (Eq. 7.7). The use of an ethanol/water system was found to be the best in terms of both yield and product isolation. The use of organic solvent such as chloroform resulted in oxidized byproducts.17... 

The reaction of indole and /V-mcthylpyrrole via Friedel-Crafts reactions with 0CHC02Et in various aqueous solutions generated substituted indoles and pyrroles without using any metal catalyst (Eq. 7.8).18... 

The second method leads to the formation 3-alkyl- and 3-arylindoles from the reaction of indole with aldehydes in the presence of alkali metal tetra-carbonylhydridoferrate (Scheme 40).67 It is possible that this novel process may occur via reduction of intermediate 3-alkylidene- or 3-arylidene indolenines. 

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