Indoles, both naturally occurring and synthetic, exhibit wide-ranging biological activity. Unusual and complex molecular architectures occur among their natural derivatives. As a result, this important ring system continues to attract attention from the international chemical community, and new methodologies for the construction of this ever relevant heteroaromatic ring continue to be developed. Unfortunately, many methods frequently start from ortho-substituted anilines, thereby greatly restricting the availability of starting materials. A more general approach would start from a mono-functionalized arene such as an aniline or halobenzene, followed by cyclization with C–C or C–N bond formation to an unactivated C–H bond. Such methods are the subject of this perspective.

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Chemia%20heterocyklickych%20zlucenin/Prednaska%202/Doplnkove%20studijne%20materialy/Indole/Indole%20synthesis%20%96%20something%20old,%20something%20new.pdf

Indole synthesis – something old, something new

Fishing for complements! There is an alternative to the useful Fischer indole synthesis. The new method utilizes the same retrosynthetic disconnection but is based on a Rh(III) -catalyzed directed CH activation step and a successive coupling with alkynes.

Indole synthesis by rhodium(III)-catalyzed hydrazine-directed C-H activation: redox-neutral and traceless by N-N bond cleavage.

Indoles are the most abundant heterocycles in biologically active natural products, pharmaceuticals, agrochemicals, and are relevant substructures in functional materials. As a result, the development of methodologies that enable the synthesis of these compounds is continuously demanded. This review summarizes most recent and relevant approaches towards the preparation of this prevalent structural motif.

Recent advances in indole syntheses: New routes for a classic target

Batting the ylides: A simple procedure carried out under mild conditions allows the direct and efficient synthesis of structurally diverse indoles. This approach involves a cascade reaction of sulfur ylides and N-(ortho-chloromethyl)aryl amides.

Synthesis of Indoles through Highly Efficient Cascade Reactions of Sulfur Ylides and N-(ortho-Chloromethyl)aryl Amides

Organic Compounds David Tilly,† Floris Chevallier,† Florence Mongin,*,† and Philippe C. Gros*,‡,§ †Equipe Chimie et Photonique Molećulaires, Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite ́ de Rennes 1, Bat̂iment 10A, Case 1003, Campus de Beaulieu, Avenue du Geńeŕal Leclerc, 35042 Rennes Ced́ex, France ‡HECRIN, Universite ́ de Lorraine, SRSMC UMR 7565, Boulevard des Aiguillettes, 54506 Vandoeuvre-les̀-Nancy, France HECRIN, CNRS, SRSMC UMR 7565, Boulevard des Aiguillettes, 54506 Vandoeuvre-les̀-Nancy, France

Bimetallic combinations for dehalogenative metalation involving organic compounds.

Primary and secondary alkylzinc reagents add to various aryldiazonium salts leading to polyfunctional indoles by means of a [3,3]-sigmatropic shift and subsequent aromatization.

Fischer Indole Synthesis with Organozinc Reagents

Fischer‐Indolsynthese mit Organozinkreagentien

Functionalized organozinc reagents readily react with various aryldiazonium salts furnishing regioselectively polyfunctional indoles after heating with microwave irradiation. This new organometallic variation of the Fischer indole synthesis tolerates a wide range of functional groups and can be readily scaled up.

Efficient Preparation of PolyfunctionalIndoles via a Zinc Organometallic Variation of the FischerIndole Synthesis

Functionalized organozinc substrates are prepared following different metalation strategies and subjected to the reaction with various aryldiazonium salts.

Zhi‐Guang Zhang

Papers

Fischer Indole Synthesis with Organozinc Reagents

Fischer‐Indolsynthese mit Organozinkreagentien

Efficient Preparation of PolyfunctionalIndoles via a Zinc Organometallic Variation of the FischerIndole Synthesis

Efficient Preparation of Polyfunctional Indoles via a Zinc Organometallic Variation of the Fischer Indole Synthesis.

Fischer Indole Synthesis with Organozinc Reagents.