Indoles and Indolizines

The indole ring system is probably the most ubiquitous heterocycle in a large number of biologically active natural products and pharmaceutical agents. Unsurprisingly, the synthesis and fimctionalization of indoles have been the subjects of much research and various well-established classical methods have become available since the structure of indole was elucidated by Baeyer and Knop in 1866.  

Compared with multi-steps used to form the desired l-azabicyclo[4.3.0]no-nane framework, Basavaiah and Rao have reported a novel, facile, convenient methodology for the synthesis of indolizines in a one-pot operation that was the first example of an electrophile-induced MBH reaction. The treatment of pyridine-2-carbaldehyde with various activated alkenes in the presence of 

Following the synthesis of substituted indole A-oxides via a TiC -mediated MBH reaction of a-oxo cyclic ketene-S ,iS -acetal with 2-nitrobenzaldehydes, Dong and Liu and their co-workers further developed a novel method to rapidly synthesize indolizines from MBH adducts 509, which in turn were prepared from the reaction of a-EWG ketene S ,A-acetals with 2-pyridinecarbaldehyde 

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Breakthroughs in Indole and Indolizine Chemistry- New Synthetic Pathways, New Applications... 

Different strategies for generating diverse collections of small molecules with indole and indolizine moieties have been developed. They can be S3mthesized by means of classical and nonclassical pathways. 

The development of simple, convenient, and an eco-friendly approach for the S3mthesis of these biologically imporiant compoimds is still in demand. For example, the very useful and green concept of a "click" reaction is a facile, selective, high-peld reaction imder mild water-tolerant conditions with little or no by-products [8]. Cascade armulation reactions lead also to the formation of polycydic fused six- and seven-membered heterocycles with indole and indolizine core [9]. 

Both indoles and indolizines could be functionalized via alkylation with enamides under mild conditions (Figures 19 and 20), using Feds, in short reaction times with good yields [2]. 

As we have seen so far, interesting pathways have been proposed for the S3mthesis of indoles and indolizines. Many of these molecules have subsequently been involved in tests to assess their biological activity. Natural compoimds with these moieties have also attracted interest, not just as extracts, but as targets for total/semisynthesis or as frameworks for compound libraries. Next, we shall review some of the extremely diverse pharmaceutical appHcations of these derivatives, ranging from fluorescence probes, to antiviral, to anticancer molecules currently in clinical trials. 

Considering the growing interest for biologically active compounds, we believe that in the future the search for novel indole and indolizine derivatives wUl result in the emergence of... 

With the remarkable number of approved indole-containing drugs as well as the importance of the indolizine moiety, it can be easily concluded that indole and indolizine derivatives offer perspectives on how p)rrrole scaffolds might be exploited in the future as bioactive molecules against a broad range of diseases. 

Chernyak N, Tilly D, Li Z and Gevorgyan V. Cascade carbopalladation-annulation approach toward polyciclic derivatives of indole and indolizine. ARKIVOC. 2011 76-91. 

A stepwise process, via hydrogen migration tautomers arriving at the same products, has been shown by density-functional theory to be responsible for the observed products of indole pyrolysis. 3-Phenyl-3-nitrosoindole, on activation with benzoyl chloride, has been found to react with indoles and indolizines (as nucleophiles) to afford products of 1,2-addition which can undergo a 1,3-nucleophilic migration in... 

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