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Catalytic Asymmetric Reactions of 4‐Substituted Indoles with Nitroethene: A Direct Entry to Ergot Alkaloid Structures
Author(s) -
Romanini Simone,
Galletti Emilio,
Caruana Lorenzo,
Mazzanti Andrea,
Himo Fahmi,
Santoro Stefano,
Fochi Mariafrancesca,
Bernardi Luca
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502655
Subject(s) - chemistry , indole test , nucleophile , nitro , catalysis , adduct , protonation , ring (chemistry) , friedel–crafts reaction , medicinal chemistry , phosphoric acid , organocatalysis , stereochemistry , organic chemistry , enantioselective synthesis , ion , alkyl
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.