Expanded Indacene-Tetrathiafulvalene Scaffolds: Structural Implications for Redox Properties and Association Behavior.

Redox-controlled dimerization of tetrathiafulvalene (TTF) derivatives is an important tool for achieving reversible assemblies. Herein, the synthesis and characterization of indacene-TTF hybrids, in which the central core is fused to naphtho or benzothieno units, are reported. The orientation of these units has a strong influence on the redox properties, with regard to the number of electrons involved in the first oxidation event and the ability of the oxidized forms to associate. The formation of mixed-valence and π-dimer complexes is turned off for those systems in which geometrical constraints provide nonplanar π-systems. Introduction of bulky substituents presents another way of preventing association, as revealed by studies of indenofluorene and diindenoanthracene scaffolds with (triisopropylsilyl)ethynyl groups. Horner-Wadsworth-Emmons reactions present a general synthetic protocol to access superextended TTFs, by using diones of polycyclic conjugated hydrocarbons as substrates.

Synthesis of the Unknown Indeno[1,2-a]fluorene Regioisomer: Crystallographic Characterization of Its Dianion.

Of the five possible indenofluorene regioisomers, examples of a fully conjugated indeno[1,2-a]fluorene scaffold have so far remained elusive. This work reports the preparation and characterization of 7,12-dimesitylindeno[1,2-a]fluorene as a highly reactive species. Experimental and computational data support the notion of a molecule with pronounced diradical character that exists in a triplet ground state. As such, both NICS and ACID calculations suggest that the indeno[1,2-a]fluorene scaffold is weakly Baird aromatic. Reduction of the unstable red solid with Cs metal produces the dianion of the title compound, from which single crystals could be obtained and X-ray data acquired, thus fully corroborating the proposed indeno[1,2-a]fluorene hydrocarbon core.

Synthesis and Characterization of Two Unsymmetrical Indenofluorene Analogues: Benzo[5,6]-s-indaceno[1,2-b]thiophene and Benzo[5,6]-s-indaceno[2,1-b]thiophene.

The synthesis and characterization of two benzo-indaceno-thiophene compounds (anti-BIT and syn-BIT) are described. Two sequential Suzuki cross-couplings utilizing the halogen selectivity of this reaction permit modular assembly of unsymmetrical indeno[1,2-b]fluorene analogues. Analysis of their cyclic voltammetry and UV-vis spectra reveal that the optical and electrochemical properties of the BITs lie between those of indeno[1,2-b]fluorenes and indacenodithiophene.

Two BN isosteres of anthracene: synthesis and characterization.

The synthesis of two parental BN anthracenes, 1 and 2, was developed, and their electronic structure and reactivity behavior were characterized in direct comparison with all-carbon anthracene. Gas-phase UV-photoelecton spectroscopy studies revealed the following HOMO energy trend: anthracene, -7.4 eV; BN anthracene 1, -7.7 eV; bis-BN anthracene 2, -8.0 eV. The λmax of the lower energy band in the UV-vis absorption spectrum is as follows: anthracene, 356 nm; BN anthracene 1, 359 nm; bis-BN anthracene 2, 357 nm. Thus, although the HOMO is stabilized with increasing BN incorporation, the HOMO-LUMO band gap remains unchanged across the anthracene series. The emission λmax values for the three investigated anthracene compounds are at 403 nm. The pKa values of the N-H proton for BN anthracene 1 and bis-BN anthracene 2 were determined to be approximately 26. BN anthracenes 1 and 2 do not undergo heat- or light-induced cycloaddition reactions or Friedel-Crafts acylations. Electrophilic bromination of BN anthracene 1 with Br2, however, occurs regioselectively at the 9-position. The reactivity behavior and regioselectivity of bromination of BN anthracenes are consistent with the electronic structure of these compounds; i.e., (1) the lower HOMO energy levels for BN anthracenes stabilize the molecules against cycloaddition and Friedel-Crafts reactions, and (2) the HOMO orbital coefficients are consistent with the observed bromination regioselectivity. Overall, this work demonstrates that BN/CC isosterism can be used as a molecular design strategy to stabilize the HOMO of acene-type structures while the optical band gap is maintained.

BN/CC isosteric compounds as enzyme inhibitors: N- and B-ethyl-1,2-azaborine inhibit ethylbenzene hydroxylation as nonconvertible substrate analogues.

Good substrate gone bad! BN/CC isosterism of ethylbenzene leads to N-ethyl-1,2-azaborine and B-ethyl-1,2-azaborine. In contrast to ethylbenzene, which is the substrate for ethylbenzene dehydrogenase (EbDH), N-ethyl-1,2-azaborine (see scheme; Fc=Ferricenium tetrafluoroborate) and B-ethyl-1,2-azaborine are strong inhibitors of EbDH. Thus, the changes provided by BN/CC isosterism can lead to new biochemical reactivity.

Kilo-Scale GMP Synthesis of Renewable Semisynthetic Vaccine-Grade Squalene.

Emulsions of the triterpene squalene ((6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, CAS 111-02-4) have been used as adjuvants in influenza vaccines since the 1990s. Traditionally sourced from shark liver oil, the overfishing of sharks and concomitant reduction in the oceanic shark population raises sustainability issues for vaccine adjuvant grade squalene. We report a semisynthetic route to squalene meeting current pharmacopeial specifications for use in vaccines that leverages the ready availability of trans-ß-farnesene ((6E)-7,11-dimethyl-3-methylene-1,6,10-dodecatriene, CAS 18794-84-8), manufactured from sustainable sugarcane via a yeast fermentation process. The scalability of the proposed route was verified by a kilo-scale GMP synthesis. We also report data demonstrating the synthesized semi-synthetic squalene's physical stability and biological activity when used in a vaccine adjuvant formulation.

Reductive Aromatization/Dearomatization and Elimination Reactions to Access Conjugated Polycyclic Hydrocarbons, Heteroacenes, and Cumulenes.

Acenes, heteroacenes, conjugated polycyclic hydrocarbons, and polycyclic aromatic hydrocarbons (collectively referred to in this review as conjugated polycyclic molecules, CPMs) have fascinated chemists since they were first isolated and synthesized in the mid 19th century. Most recently, these compounds have shown significant promise as the active components in organic devices (e.g., solar cells, thin-film transistors, light-emitting diodes, etc.), and, since 2001, a plethora of publications detail synthetic strategies to produce CPMs. In this review, we discuss reductive aromatization, reductive dearomatization, and elimination/extrusion reactions used to form CPMs. After a brief discussion on early methods to synthesize CPMs, we detail the use of reagents used for the reductive (de)aromatization of precursors containing 1,4-diols/diethers, including SnCl2 and iodide (I- ). Extension of these methods to carbomers and cumulenes is briefly discussed. We then describe low-valent metal species used to reduce endoxides to CPMs, and discuss the methods to directly reduce acenediones and acenones to the respective acene. In the final section, we describe methods used to affect aromatization to the desired CPM via extrusion of small, volatile molecules.

Indacenodibenzothiophenes: synthesis, optoelectronic properties and materials applications of molecules with strong antiaromatic character.

Indeno[1,2-b]fluorenes (IFs), while containing 4n π-electrons, are best described as two aromatic benzene rings fused to a weakly paratropic s-indacene core. In this study, we find that replacement of the outer benzene rings of an IF with benzothiophenes allows the antiaromaticity of the central s-indacene to strongly reassert itself. Herein we report a combined synthetic, computational, structural, and materials study of anti- and syn-indacenodibenzothiophenes (IDBTs). We have developed an efficient and scalable synthesis for preparation of a series of aryl- and ethynyl-substituted IDBTs. NICS-XY scans and ACID calculations reveal an increasingly antiaromatic core from [1,2-b]IF to anti-IDBT, with syn-IDBT being nearly as antiaromatic as the parent s-indacene. As an initial evaluation, the intermolecular electronic couplings and electronic band structure of a diethynyl anti-IDBT derivative reveal the potential for hole and / or electron transport. OFETs constructed using this molecule show the highest hole mobilities yet achieved for a fully conjugated IF derivative.

Diindeno-fusion of an anthracene as a design strategy for stable organic biradicals.

The consequence of unpaired electrons in organic molecules has fascinated and confounded chemists for over a century. The study of open-shell molecules has been rekindled in recent years as new synthetic methods, improved spectroscopic techniques and powerful computational tools have been brought to bear on this field. Nonetheless, it is the intrinsic instability of the biradical species that limits the practicality of this research. Here we report the synthesis and characterization of a molecule based on the diindeno[b,i]anthracene framework that exhibits pronounced open-shell character yet possesses remarkable stability. The synthetic route is rapid, efficient and possible on the gram scale. The molecular structure was confirmed through single-crystal X-ray diffraction. From variable-temperature Raman spectroscopy and magnetic susceptibility measurements a thermally accessible triplet excited state was found. Organic field-effect transistor device data show an ambipolar performance with balanced electron and hole mobilities. Our results demonstrate the rational design and synthesis of an air- and temperature-stable biradical compound.

Synthesis and Properties of Fully-Conjugated Indacenedithiophenes.

The synthesis and characterization of four fully-conjugated indacenedithiophenes (IDTs) are disclosed. In contrast to anthradithiophenes, regioselective synthesis of both syn and anti isomers is readily achieved. Thiophene fusion imparts increased paratropic character on the central indacene core as predicted by DFT calculations and confirmed by 1H NMR spectroscopy. IDTs exhibit red-shifted absorbance maxima with respect to their all-carbon analogues and undergo two-electron reduction and one-electron oxidation.

Diazaheterocycle analogues of tetracene: synthesis and properties of a naphtho-fused cinnoline and a naphtho-fused isoindazole.

The synthesis and characterization of a diethynyl naphtho-fused cinnoline and isoindazole are described. The results show that both electron-accepting and electron-donating molecules can be prepared from a common intermediate.