Extended Multicomponent Reactions with Indole Aldehydes: Access to Unprecedented Polyheterocyclic Scaffolds, Ligands of the Aryl Hydrocarbon Receptor. Issue 5 (26th November 2020)

• Record Type: Journal Article
• Authors: Ghashghaei, Ouldouz; Pedrola, Marina; Seghetti, Francesca; Martin, Victor V.; Zavarce, Ricardo; Babiak, Michal; Novacek, Jiri; Hartung, Frederick; Rolfes, Katharina M.; Haarmann‐Stemmann, Thomas; Lavilla, Rodolfo
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 5(2021)
• Page Start: 2603
• Page End: 2608
• Publication Date: 2020-11-26
• Subjects: domino reactions -- multicomponent reactions -- nitrogen heterocycles -- receptors -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202011253
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The participation of reactants undergoing a polarity inversion along a multicomponent reaction allows the continuation of the transformation with productive domino processes. Thus, indole aldehydes in Groebke–Blackburn–Bienaymé reactions lead to an initial adduct which spontaneously triggers a series of events leading to the discovery of novel reaction pathways together with direct access to a variety of linked, fused, and bridged polyheterocyclic scaffolds. Indole 3‐ and 4‐carbaldehydes with suitable isocyanides and aminoazines afford fused adducts through oxidative Pictet–Spengler processes, whereas indole 2‐carbaldehyde yields linked indolocarbazoles under mild conditions, and a bridged macrocycle at high temperature. These novel structures are potent activators of the human aryl hydrocarbon receptor signaling pathway. Abstract : By engaging indole aldehydes in an isocyanide multicomponent reaction, the polarity inversion of the indole moiety along the transformation triggers an extension of the domino process, leading to a variety of unprecedented fused, linked, and bridged scaffolds. The processes can be run in parallel and the adducts display remarkable bioactivity as potent ligands of the aryl hydrocarbon receptor.