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image of Indole-Based [3+2] Annulations: Strategies for Complexity Construction - A Literature Review

Abstract

Indole-based organic compounds have attracted widespread interest due to their phenomenal chemical characteristics. Among these, the [3+2] annulation is a highly valuable reaction for generating complexity and valuable synthons in organic synthesis. The [3+2] annulation of the indole ring opens new avenues for synthesizing a wide range of functionalised indole derivatives. Further, these derivatives are highly valued in synthetic and medicinal chemistry due to their unique structural features and broad chemical reactivity. The indole scaffold is commonly found in natural products and pharmaceuticals, making it a privileged structure in drug design. Among the various synthetic approaches, the [3+2] annulation reactions have emerged as a powerful method for building complex annulated indole derivatives. Notwithstanding these reactions, which typically involve a 1,3-dipolar species and the electron-rich indole core, enable rapid construction of five-membered fused ring systems and introduce diverse functional groups in a single step. This strategy not only enhances molecular complexity but also facilitates access to bioactive intermediates with desirable medicinal applications. Indole-based [3+2] annulated compounds exhibit a wide range of biological activities, including antibacterial, antifungal, antioxidant, anticancer, and anti-inflammatory effects. These properties can be fine-tuned by modifying the substituents on the indole ring, making them attractive candidates for therapeutic development. The broad spectrum of biological activities and its potential for further functionalization motivate scientists and researchers to explore, develop novel methodologies and identify new lead compounds to foster drug discovery developments. Ongoing research focuses on developing new annulation protocols, optimizing conditions, and designing novel catalysts to expand the diversity of indole-based libraries. These compounds show promise not only as pharmaceutical leads but also as valuable tools in biological research and agrochemicals.

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2026-01-19
2026-01-31

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Indole-Based [3+2] Annulations: Strategies for Complexity Construction - A Literature Review
Bentham Science Publishers ; https://doi.org/10.2174/0118756298398029251110075039
/content/journals/mroc/10.2174/0118756298398029251110075039
/content/journals/mroc/10.2174/0118756298398029251110075039
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  • Article Type:     Review Article
Keywords: cycloaddition ; Indole ; pyrrolidines ; annulation ; antioxidant ; agrochemicals

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