Iron-catalyzed regioselective C-H alkylation of indoles: an additive-free approach in renewable solvent

Alkylated indoles are important motifs in various biologically active molecules and drug candidates. Herein, we report a mild and efficient iron-catalyzed protocol for synthesizing alkylated indoles via C-H bond alkylation of indoles with unactivated alkenes, demonstrating a high level of regioselec...

Full description

Saved in:
Bibliographic Details
Published in:Green chemistry : an international journal and green chemistry resource : GC 2023-11, Vol.25 (23), p.9733-9743
Main Authors: Pradhan, Chandini, Jagtap, Rahul A, Samal, Pragnya Paramita, Krishnamurty, Sailaja, Punji, Benudhar
Format: Article
Language:English
Subjects:
Alkenes
Alkylation
Biological activity
Catalysts
Chemical synthesis
Drug development
Green chemistry
Hydrogen bonds
Indoles
Iron
Organometallic compounds
Regioselectivity
Siloxanes
Solvents
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Alkylated indoles are important motifs in various biologically active molecules and drug candidates. Herein, we report a mild and efficient iron-catalyzed protocol for synthesizing alkylated indoles via C-H bond alkylation of indoles with unactivated alkenes, demonstrating a high level of regioselectivity. The reaction occurs under additive-free, solvent-free (or trace green solvent, 2-MeTHF) and less energy-intensive conditions using a sustainable metal catalyst and provides easy access to privileged alkylated indoles with anti-Markovnikov selectivity. Alkylation is compatible with important functionalities, such as fluoro, chloro, trifluoromethyl, alkenyl, ether, thioether, silyl, and siloxane, including heteroaryl, pyridinyl, carbazolyl, and indolyl moieties (45 examples, up to 96% yield). The developed protocol is very simple, straightforward, and fully accords with the principles of green chemistry. A detailed mechanistic investigation manifests the facile indole's C-H activation at the Fe(0) center, reversible 1,2-insertion of the alkene into the Fe-H bond of a metallacycle, and a turnover-limiting reductive elimination. Alkylated indoles are important motifs in various biologically active molecules and drug candidates.
ISSN:1463-9262
1463-9270
DOI:10.1039/d3gc03709f