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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. 

Inclusion of a fused pyridine ring onto the core motif of an azaphosphinine heterocycle, as well as functionalization with an N-acetamide group, furnishes a chiral, quadruple hydrogen bonding face that is capable of strong homodimerization. Eleven different azaphosphinine derivatives were prepared with variable electron donor and acceptor functionalization. Contrary to simple DA azaphosphinine dimers, trends from substituent effects showed that the hydrogen bond acceptors (A) were more sensitive to the substituents than the hydrogen bond donors (D). With electron donating groups appended onto the azaphosphinine scaffold, dimerization constants rose to as high as 209 M–1 in 10% DMSO in water-saturated CDCl3 . X-ray crystallographic data unexpectedly showed that the quadruply hydrogen bonding system preferred the theoretically less stable donor-acceptor-donor-acceptor (DADA) H-bond orientation despite having the capability to tautomerize to the potentially more stable DDAA structure. Computational analysis revealed that maintaining pyridine aromaticity was more stabilizing than the secondary interactions that would be created from a DDAA dimer. Additionally, these molecules associate as the first examples of R,R- and S,S-azaphosphinine homodimers, compared to the R,S-heterodimers typically found for simple azaphosphinines. This observation was explained by computational analysis, which found a geometric difference between the nitrogen atoms adjacent to the phosphorus chiral center of the Homo and Hetero dimer, leading to a stronger hydrogen bonding interaction in the Homo dimer. Further understanding of this quadruply hydrogen bonding core will allow us to explore further applications that integrate this strongly hydrogen bonding system into larger and more complex supramolecular frameworks such as supramolecular polymers or capsules. 

Abstract Thiol‐disulfide interchange has been a large field of study for both biochemists and physical organic chemists alike due to its prevalence within biological systems and fundamentally interesting dynamic nature. More recently, efforts have been made to harness the power of this reversible reaction to make self‐assembling systems of macrocyclic molecules. However, less effort has focused on the fundamental work of isolating these assemblies and studying the factors that control the assembly and sorting of these emerging cyclic systems. A more complete fundamental understanding of factors controlling such self‐assembly could also improve understanding of the complex systems biology of thiol exchange while also aiding in the design of dynamic thiol assembly to enable applications ranging from drug delivery and biosensing to new materials synthesis. We have shown previously that pnictogen‐assisted self‐assembly enables formation of discrete disulfide macrocycles and cages without competition from polymer formation for a wide variety of alkyl thiols. In this study, we report the expansion of pnictogen‐assisted self‐assembly methods to form disulfide bearing macrocycles from aryl thiol containing ligands, allowing access to previously unreported molecules. These studies complement classical physical organic and chemical biology studies on the rates and products of aryl thiol oxidation to disulfides, and we show that this self‐assembly method revises some prevailing wisdom from these key classical studies by providing new product distributions and new isolable products in cyclic disulfide formation. 

Abstract Herein we report the synthesis and characterization of four donor/acceptor‐fuseds‐indacenes via the late‐stage oxidation of a family of unsymmetrical benzofuran/benzothiophene‐s‐indacene regioisomers. A thorough study of their properties through experimental and computational analysis has revealed the effect of asymmetry on the molecular properties associated with antiaromaticity, as well as a strong correlation between antiaromaticity and intramolecular charge transfer (ICT). The strength of the charge transfer depends on the fusion orientation of the donor and acceptor motifs relative to thes‐indacene core. The two most antiaromatic oxidized isomers exhibit strong evidence of ICT with 30 and 40 nm solvatochromic shifts. 

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.