From [10]Paracyclophane to Ferrocenophanones: The Search for Molecular Machines and Bio-Organometallic Anticancer Drugs

A partial quenching of the NMR ring current in [10]paracyclophane-chromium tricarbonyl prompted a study of other metal–arene π complexes, several of which exhibited restricted intramolecular motion relevant to their potential use in molecular machines. An attempted Diels–Alder reaction of 9-phenylethynyl-9H-fluorene with tetracyclone instead yielded a novel tetracene by isomerization of the alkyne to the corresponding allene, and then via a series of allene dimers which are classifiable as cyclophanes. (Subsequently, the first organometallic molecular brake was prepared, whereby migration of a metal carbonyl tripod over an indenyl framework blocked the rotation of a triptycene paddlewheel.) Cyclophanes have now found applicability in the field of bio-organometallic chemistry; the activity of tamoxifen, the first line treatment for hormone-dependent breast cancers, is markedly enhanced when the structure is modified by incorporation of a ferrocenophane moiety. Finally, we relate the story of how the first cyclophane, [1.1.1]orthocyclophane, was actually prepared by Cannizzaro in 1854, but was only recognized as such more than 150 years later.