Iron‐Catalyzed Reductive Cyclization by Hydromagnesiation: A Modular Strategy Towards N‐Heterocycles. (7th September 2021)

• Record Type: Journal Article
• Authors: Loup, Joachim; Larin, Egor M.; Lautens, Mark
• Is Part Of: Angewandte Chemie. Volume 133:Number 41(2021)
• Page Start: 22519
• Page End: 22525
• Publication Date: 2021-09-07
• Subjects: hydromagnesiation -- indole -- iron catalysis -- oxindole -- reductive cyclization; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202106996
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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. Abstract : An iron‐catalyzed reductive cyclization of 2‐vinylanilides to prepare a variety of N ‐heterocycles is reported. The reaction, which usually occurs at room temperature over a short reaction time, employs an inexpensive and bench‐stable iron catalyst and EtMgBr as a hydride source. The breadth of this strategy was demonstrated by the synthesis of densely substituted indoles, oxindoles and novel tetrahydrobenzoazepinoindolones, as well as the application towards the formal syntheses of bioactive compounds.