Multicomponent Synthesis on a Diiron Platform of Stable Ferrabenzenes with Promising Anticancer Activity

Area of Science:

• Organometallic Chemistry
• Synthetic Chemistry

Background:

• Ferrabenzenes, analogues of benzene containing an iron atom, are rare and challenging to synthesize.
• Previous synthesis of ferrabenzenes was accidental, hindering further research.

Purpose of the Study:

• To develop a reproducible synthetic route to substituted ferrabenzenes.
• To investigate the properties and potential applications of newly synthesized ferrabenzenes.

Main Methods:

• A one-pot double C─C coupling reaction involving iminium, carbene, and carbon monoxide moieties.
• O-alkylation of ferra-cyclohexadienone intermediates.
• Characterization using X-ray crystallography, NMR, IR spectroscopy, and mass spectrometry.
• Computational studies to elucidate reaction mechanisms and aromaticity.

Main Results:

• A class of four substituted ferrabenzenes (5a-c) were synthesized and stabilized by η⁶-coordination.
• Experimental and computational data confirmed the aromatic character of the ferrabenzene ring.
• Selected ferrabenzenes demonstrated air stability, aqueous solubility, and a balanced hydrophilic/lipophilic profile.
• These compounds exhibited potent in vitro cytotoxicity against cancer cell lines, with notable selectivity.

Conclusions:

• A reliable method for synthesizing ferrabenzenes was established.
• The synthesized ferrabenzenes possess favorable physicochemical properties for potential biological applications.
• Ferrabenzenes show significant promise as anti-cancer agents due to their cytotoxicity and selectivity.