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Ferrocenes were studied as cyclopentadiene ring surrogates enroute to non-metallocene targets such as the aminofulveno[1,2-b]chromone natural product chalaniline A. Ferroceno[b]chromone, as an archetype of interest, was prepared from ferrocenecarboxylic acid (4 steps, 24% yield) via N,N-diethyl 2-iodoferrocenecarboxamide by Ullmann etherification with phenol followed by LDA-mediated anionic cyclization. Reactivity studies revealed that this planar chiral analogue of xanthone readily fragments into non-metallocene products upon reaction with electrophiles. 1-Methoxy-3-methylferroceno[b]chromone, prepared similarly by substituting O-methylorcinol for phenol, was advanced to chalaniline A and a transposed regioisomer by concomitant deferration and demethylation with AlCl3; formylation of the resulting cyclopentadiene-fused chromone with excess Vilsmeier reagent; and then Pinnick oxidation (NaClO2), methylation (TMSCHN2), and final transamination (PhNH2). Four compounds, including ferroceno[b]chromone and the C11/C12-transposed regioisomer of chalaniline A, were characterized by single crystal X-ray diffraction analysis. 

Chalaniline A, an aminofulveno[1,2-b]chromone derivative previously isolated from a vorinostat-treated ascomycete Chalara sp., was prepared in nine steps from orcinol (3,5- dihydroxytoluene). In a key transformation, the tricyclic ring system of the target was generated by a pyrrolidine-catalyzed double annulation between α-(methylsulfinyl)-2,6-dihydroxy-4-methylacetophenone and the ketaldoester, methyl 2,5-dioxopentanoate. The resulting tertiary alcohol (coniochaetone H) was further converted to chalaniline A by operations including dehydration (to yield a hydroxyfulvene), Vilsmeier reaction, and enamine exchange.