Indole—continued 3-substituted, synthesis

New approaches to the indole nucleus are continuously developed, providing aceess to indoles which are difficult to prepare using the well established reactions, such as the Fischer indole synthesis. Nevertheless, this classic reaction is still often used for constructing more complex systems, as exemplified by the preparation of 2-(pyrimidin-4-yl)indoles <03CPB975>, or indolo[3,2-i)]carbazoles possessing new substitution patterns <03T1265>. 

Many examples of Diels-Alder reactions have been carried out on quinodimethanes derived in a variety of ways from pyrrole and indole precursors. This area continues to be widely investigated because of its generality and its synthetic utility. In the case of pyrrole derivatives, this methodology leads to the synthesis of indoles, and particularly those substituted in the benzene ring. 

Radical reactions are now a well-established and commonly used methodology for the synthesis of heterocycles and indoles in particular. Tributyltin hydride mediated radical reactions including additions, substitutions, and cyclizations continue to he... 

In Chap. 3, Sundberg, an indole pioneer and the author of the 1970 classic monograph The Chemistry of Indoles , covers thoroughly Electrophilic Substitution Reactions of Indoles , which is probably the most ubiquitous reaction of indole and one that continues to be extraordinarily useful in synthesis. 

Seeberger and coworkers reported the synthesis of indoles and related heterocycles by continuous flow thermolysis of azidoacrylates under high temperature and pressure [64]. 2-Methoxycarbonyl-substituted indole was obtained in a good yield at 220 °C and 22.5 bar (Scheme 5.46). Gram scale synthesis of a precursor of D-amino acid oxidase (DAAO) inhibitor was also demonstrated. 

Wahab B., Ellames G., Passey S., Watts P. Synthesis of substituted indoles using continuous flow micro reactors. Tetrahedron 2010 66(21) 3861-3865. 

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