Ferrocene-Templated Synthesis of Fused Aminofulvenes: Elaboration of Chalaniline A and a Reversed Regioisomer via a Ferroceno[b]chromone

Abstract 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.