Trapping para-Quinone Methide Intermediates with Ferrocene: Synthesis and Preliminary Biological Evaluation of New Phenol-Ferrocene Conjugates

The reaction of para-hydroxybenzyl alcohols with ferrocene in the presence of a catalytic amount of InCl(3) provided ferrocenyl phenol derivatives, an interesting class of organometallic compounds with potential applications in medicinal chemistry. This transformation exhibited a reasonable substrate scope delivering the desired products in synthetically useful yields. Evidence of involvement of a para-quinone methide intermediate in this coupling process was also provided. Preliminary biological evaluation demonstrated that some of the ferrocene derivatives available by this methodology exhibit significant cytotoxicity against several cancer cell lines with IC(50) values within the range of 1.07–4.89 μM.