Catalytic Asymmetric Reactions of 4-Substituted Indoles with Nitroethene: A Direct Entry to Ergot Alkaloid Structures.
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.
Department of Industrial Chemistry "Toso Montanari", University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy).
Simone
S
Romanini
Department of Industrial Chemistry "Toso Montanari", University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy).
Emilio
E
Galletti
Department of Industrial Chemistry "Toso Montanari", University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy).
Lorenzo
L
Caruana
Department of Industrial Chemistry "Toso Montanari", University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy).
Andrea
A
Mazzanti
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 10691 Stockholm (Sweden).
Fahmi
F
Himo
Department of Chemistry, Biology and Biotechnology, University of Perugia, V. Elce di Sotto 8, 06123 Perugia (Italy). stefano.santoro@unipg.it.
Stefano
S
Santoro
Department of Industrial Chemistry "Toso Montanari", University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy). mariafrancesca.fochi@unibo.it.
Mariafrancesca
M
Fochi
Department of Industrial Chemistry "Toso Montanari", University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy). luca.bernardi2@unibo.it.
Luca
L
Bernardi
Brønsted acids; asymmetric synthesis; indoles; nitroalkenes; organocatalysis