Synthesis and Structural Characterization of Ferrocenyl-Substituted Aurones, Flavones, and Flavonols

In the context of our studies on the modification of bioactive molecules with ferrocene, we here report the first examples of ferrocenyl flavonoids, where ferrocene replaces the B ring of the flavonoid skeleton. Ferrocenyl aurones possessing an electron-withdrawing or an electron-donating group in the 5'-position were obtained from 5'-R-2'-hydroxy-3-ferrocenyl chalcones via 1,5 oxidative exocyclization using Hg(OAc)(2) or AgOTf. Treatment of the ferrocenyl aurones with LDA resulted in a ring opening to form ferrocenyl ynones, which could then be selectively recydized to the flavone isomer by treatment with NaOEt. Ferrocenyl flavones were also obtained by isomerization of the aurones with KCN and were hydroxylated in the 3-position to form ferrocenyl flavonols with oxone in a biphasic reaction. In many cases the reactivity of the ferrocenyl compounds was significantly different from that of their organic analogues. This reactivity and regioselectivity can be rationalized by ferrocene's particular ability to destabilize alpha-anions in reaction intermediates. Representative examples of ferrocenyl aurones, ynones, and flavones were characterized by 2D NMR and X-ray crystallography, and the molecules all show a planar arrangement of the organic skeleton with the cyclopentadienyl ring of the ferrocene group. Putative MLCT bands in the visible region are responsible for the variety of highly saturated colors observed.