Catalytic Asymmetric Reactions of 4‐Substituted Indoles with Nitroethene: A Direct Entry to Ergot Alkaloid Structures |
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Authors: | Simone Romanini Emilio Galletti Dr. Lorenzo Caruana Prof. Andrea Mazzanti Prof. Fahmi Himo Dr. Stefano Santoro Prof. Mariafrancesca Fochi Prof. Luca Bernardi |
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Affiliation: | 1. Department of Industrial Chemistry “Toso Montanari”, University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy);2. Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 10691 Stockholm (Sweden);3. Department of Chemistry, Biology and Biotechnology, University of Perugia, V. Elce di Sotto 8, 06123 Perugia (Italy) |
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Abstract: | A domino Friedel–Crafts/nitro‐Michael reaction between 4‐substituted indoles and nitroethene is presented. The reaction is catalyzed by BINOL‐derived phosphoric acid catalysts, and delivers the corresponding 3,4‐ring‐fused indoles with very good results in terms of yields and diastereo‐ and enantioselectivities. The tricyclic benzo[cd]indole products bear a nitro group at the right position to serve as precursors of ergot alkaloids, as demonstrated by the formal synthesis of 6,7‐secoagroclavine from one of the adducts. DFT calculations suggest that the outcome of the reaction stems from the preferential evolution of a key nitronic acid intermediate through a nucleophilic addition pathway, rather than to the expected “quenching” through protonation. |
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Keywords: | asymmetric synthesis Brø nsted acids indoles nitroalkenes organocatalysis |
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