Catalytic Asymmetric Reactions of 4-Substituted Indoles with Nitroethene: A Direct Entry to Ergot Alkaloid Structures
Simone Romanini1, Emilio Galletti1, Lorenzo Caruana1
1Department of Industrial Chemistry "Toso Montanari", University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy).
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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