Indole synthesis: a review and proposed classification

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

In recent years, transition metal-catalyzed direct (hetero)arylation reactions of heteroarenes with (hetero)aryl halides and pseudohalides have received significant attention as eco-friendly and economic alternatives to classical methods for the construction of heteroaryl-(hetero)aryl CC bonds by transition metal-catalyzed cross-couplings involving the use of stoichiometric amounts of organometallic reagents. This critical review with 430 references covers the results obtained in the period January 2009 to February 2013 in the area of the transition metal-catalyzed direct inter- and intramolecular (hetero)arylation reactions of heteroarenes containing one heteroatom. Particular attention has been given to illustrate chemo- and site selectivity aspects of these reactions as well applications of these CC bond forming reactions in the synthesis of pharmaceutically relevant compounds, natural products and their analogues and precursors. The most recent advancements into the mechanism(s) of these reactions have also been briefly reported.

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

Fischer indole synthesis catalyzed by novel SO3H-functionalized ionic liquids in water

α-Diazoesters were discovered to be good electrophiles in a catalytic asymmetric α-functionalization of ketones for the first time. This reaction also provided a direct and efficient method for C-N bond formation with excellent yields (up to 98%) and enantioselectivities (up to 99% ee) under mild conditions. The application of the electrophilicity of α-diazoesters opens up a novel way to access the diversity of diazo chemistry.

New Electrophilic Addition of α-Diazoesters with Ketones for Enantioselective C–N Bond Formation

Novel approach to arylhydrazones, the precursor for Fischer indole synthesis, via diazo esters derived from α-amino acid esters

Novel method for synthesis of aryl hydrazones from α-diazo esters: scope and limitations of nucleophiles

Development of novel pyrrole synthesis for the preparation of intermediates of bioactive pyrrole alkaloids

Versatile electrophiles N-acylhydrazones are synthesized via diazotization, reduction, and acylation of alpha-amino acid esters. Reduction of diazo esters with L-selectride or tributylphosphine affords the corresponding hydrazones in good yields. Both reducing agents give anti-hydrazones as the major product although the reactivity of each reductant is slightly different. The resulting hydrazones are acylated to give N-acylhydrazones, which are subjected to further reactions to give 1,3,4-oxadiazin-6-ones that serve as useful synthetic intermediates for the Diels-Alder reaction.

Masao Wada

Papers

Novel approach to arylhydrazones, the precursor for Fischer indole synthesis, via diazo esters derived from α-amino acid esters

Novel method for synthesis of aryl hydrazones from α-diazo esters: scope and limitations of nucleophiles

Development of novel pyrrole synthesis for the preparation of intermediates of bioactive pyrrole alkaloids

New Entry for Synthesis of N- Acylhydrazones, Pyridazinones, and 1,3,4-Oxadiazin-6-ones from α-Amino Acid Esters

A novel method for the synthesis of 3,4-disubstitutedpyrrole-2,5-dicarboxylates from hydrazones derived from α-diazo esters