Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells

The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised by enantioselective palladium-catalysed intramolecular direct C−H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of the novel ferrocifens with Ag₂O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 cell lines. This bioactivity arises from two mechanisms: Fenton-type chemistry and the anti-estrogenic activity associated with the tamoxifen-like structure.