Synthesis and Antiproliferative Effects of [3]Ferrocenophane Transposition Products and Pinacols Obtained from McMurry Cross-Coupling Reactions

We here report the synthesis and antiproliferative activities
of two new series of ferrocenophanes obtained from McMurry cross-coupling
reactions of [3]­ferrocenophan-1-one with benzophenone, 4-hydroxybenzophenone,
4,4′-dihydroxybenzophenone, and 4,4′-diacetylaminobenzophenone.
In addition to the main formation of olefins at reflux, tetrahedral
transposition products, resulting from a pinacolic rearrangement,
were also isolated in about 10% yields. Lowering the temperature of
the reaction to 0 °C allowed the isolation of pinacols, which
could be transformed into transposition compounds in good yields.
Three ferrocenophane compounds have been characterized by X-ray crystallography:
1-(p-hydroxyphenyl)-1-phenyl-2-oxo­[4]­ferrocenophane
(7b), 1,1-diphenyl-2-oxo[4]­ferrocenophane (7c), and 1-hydroxy-1-[1-hydroxy-1-[3]­ferrocenophanyl][3]­ferrocenophane
(12) crystallize in monoclinic P21/n, triclinic P1̅,
and monoclinic P21/c space
groups, respectively. The antiproliferative effects on hormone-independent
breast cancer cells (MDA-MB-231) of the transposition compounds are
generally lower than those of their corresponding butene analogues
(IC50 values in micromolar versus nanomolar range). In
contrast and quite surprisingly, the pinacol complexes are significantly
cytotoxic (IC50 in the nanomolar range), among the most
cytotoxic ferrocene compounds prepared so far. This antiproliferative
activity may be linked to their oxidative cleavage.