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Iron‐Catalyzed Reductive Cyclization by Hydromagnesiation: A Modular Strategy Towards N ‐Heterocycles
Author(s) -
Loup Joachim,
Larin Egor M.,
Lautens Mark
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202106996
Subject(s) - electrophile , chemistry , catalysis , combinatorial chemistry , intramolecular force , hydride , reactivity (psychology) , nucleophile , reductive elimination , organic chemistry , metal , medicine , alternative medicine , pathology
A reductive cyclization to prepare a variety of N ‐heterocycles, through the use of ortho ‐vinylanilides, is reported. The reaction is catalyzed by an inexpensive and bench‐stable iron complex and generally occurs at ambient temperature. The transformation likely proceeds through hydromagnesiation of the vinyl group, and trapping of the in situ generated benzylic anion by an intramolecular electrophile to form the heterocycle. This iron‐catalyzed strategy was shown to be broadly applicable and was utilized in the synthesis of substituted indoles, oxindoles and tetrahydrobenzoazepinoindolone derivatives. Mechanistic studies indicated that the reversibility of the hydride transfer step depends on the reactivity of the tethered electrophile. The synthetic utility of our approach was further demonstrated by the formal synthesis of a reported bioactive compound and a family of natural products.