An organoiron approach to thyroid hormone analogues

An approach to thyroid hormone analogues was proposed involving sequential substitution of cationic cyclopentadienyl(1,4-dichlorobenzene)iron(II) complexes with phenoxide/thiophenoxide and hydroxide/amine, followed by decomplexation. Although the selectivity for monosubstitution with phenolates and thiophenolates was poorer than previously observed, it was often possible to control the reaction with sterically less demanding phenolates of intermediate nucleophilicity. The subsequent introduction of a polar substituent into the monosubstituted product was successful with amine nucleophiles. A modified approach, based on the reverse order of substitution was also attempted. Whereas clean monosubstitution with hydroxide/hydroxide equivalents was unsuccessful, cyclopentadienyl(N-alkyl-1-chloro-4-aminobenzene)iron(II) complexes could be prepared in fair yields and further substituted with nucleophiles such as thiophenolates.