Diversification of Simple Arenes into Complex (Amino)cyclitols.

Highly oxygenated cyclohexanes, including (amino)cyclitols, are featured in natural products possessing a notable range of biological activities. As such, these building blocks are valuable tools for medicinal chemistry. While de novo synthetic strategies have provided access to select compounds, challenges including stereochemical density and complexity have hindered the development of a general approach to (amino)cyclitol structures. This work reports the use of arenophile chemistry to access dearomatized intermediates which are amenable to diverse downstream transformations. Practical guidelines were developed for the synthesis of natural and non-natural (amino)cyclitols from simple arenes through a series of strategic functionalization events.

Mechanochemical Scholl Reaction on Phenylated Cyclopentadiene Core: One-Step Synthesis of Fluoreno[5]helicenes.

In this study, we explore feasibility of the mechanochemical approach in the synthesis of tetrabenzofluorenes (fluoreno[5]helicenes). For this, commercially available phenylated cyclopentadiene precursors are subjected to the Scholl reaction in the solid state using FeCl3 as an oxidant and sodium chloride as the solid reaction medium. This ball milling process gave access to the 5-membered ring containing-helicenes in one synthetic step in high (95-96 %) isolated yields. The solution-phase reactions, however, were found to be moderate to low yielding in this regard (10-40 %).

Metal-Free, Hindered, Regioselective Access to Multifunctional Groups Diarylamines via SN Ar Substitution of P-Nitroso Aromatic Methyl Ether by Arylamines.

Multifunctional groups diarylamines, an innovative product, efficiently produced from arylamines and p-nitrosoanisole derivatives by intermolecular SN Ar under weak acid conditions. This SN Ar proceeds under mild reaction conditions, and more significantly, the substrates involved do not necessarily require strong electron-withdrawing groups. Moreover, this SN Ar is characterized by resistance to space crowding, tolerance to halogen and nitroso functional groups, and high regioselectivity. Mechanistic observations suggest that the SN Ar is the result of the transfer of the positive charge center of the protonated nitroso group to the p-methoxy group.

Overcrowded 14,14'-Bidibenzo[a,j]anthracenes: Challenges in Syntheses and Atypical Property of Lacking Symmetry-Breaking Charge Transfer (SBCT).

14,14'-Bidibenzo[a,j]anthracenes (BDBAs) were prepared by iridium-catalyzed annulation of 5,5'-biterphenylene with alkynes. The molecular geometries of overcrowded BDBAs were verified by X-ray crystallography. The two dibenzo[a,j]anthryl moieties are connected through the sterically hindered 14 positions, resulting in highly distorted molecular halves. The conformation with a small twist angle between two molecular halves can minimize steric conflicts between the substituents at 1 and 13 positions and the carbon atoms of the central axis, as well as steric clashes between those substituents. One such example is octafluoro-substituted BDBA, where the interplanar angle between two anthryl moieties is approximately 31° (currently the lowest reported value, cf. 81° in 9,9'-bianthracene). The intramolecular interactions and electronic couplings between two molecular halves resulted in upfield 1H NMR signals, redshifted absorption and emission bands, and a reduced HOMO-LUMO gap. Photodynamic investigations on BDBAs indicated that the formation of the conventional symmetry-breaking charge transfer (SBCT) state was suspended by restricted rocking around the central C-C bond. Such a mechanism associated with this highly constrained conformation was examined for the first time.

Prism[2]dihydrophenazines: Synthesis, Configurational Analysis, and Supramolecular Tessellation through Exo-Wall Interactions.

Macrocyclic arenes have gained considerable attention for their structural diversity and widespread applications. In this research, a new kind of macrocyclic arenes, namely prism[2]dihydrophenazines (anti-P2P20, syn-P2P20, and P2P22), composed of two dihydrophenazine derivatives subunits bridged by methylene groups, were conveniently synthesized by AlCl3-catalyzed one-pot condensation in 1,2-dichloroethane. Both anti-P2P20 and its isomer syn-P2P20 exhibited flexible and convertible conformation with narrow cavity, while P2P22 possessed rigid and rhombic-like skeleton due to the more steric hindrance on subunits. In addition, the selection of electron-deficient guest was found to influence the outside binding behavior of syn-P2P20. Fantastic regular supramolecular tessellation was fabricated by tiling of syn-P2P20 with tetrafluoro-1,4-benzoquinone (TFB) through the exo-wall interactions. Using 1,5-difluoro-2,4-dinitrobenzene (DFN) as a linker, only the regular 2D network superstructure with periodic units in a plane was obtained through cocrystallization. This work not only reports the construction of supramolecular tessellations by using prism[2]dihydrophenazines as building blocks, but also provides a new perspective for the design of macrocyclic arenes and fabrication of 2D supramolecular materials.

Unusually Short H⋠⋠⋠H Contacts in Intramolecularly Cyclized Helically Fused Anthracenes.

The intramolecular coupling of dichloro-substituted helically fused anthracenes using the Yamamoto coupling yielded cyclized products with sterically congested molecular structures. The X-ray analysis and DFT calculations showed that the aromatic framework adopted a nonplanar structure with a twisted conformation about the newly formed single bond, which acts as a chiral axis. Interestingly, the X-ray structure obtained through the Hirshfeld atom refinement revealed short interatomic distances between the inner hydrogen atoms (1.648-1.692 Å), much shorter than the sum of their van der Waals radii. Owing to these unusually short contacts, the 1H NMR spectrum exhibited a significant deshielding (12.5 ppm) and a large nuclear Overhauser effect (44 %). Additionally, the IR spectrum displayed a high-frequency shift of the C-H stretching vibration. These observations, along with the noncovalent interaction plot indicative of a characteristic steric environment, strongly support the presence of steric hindrance. Moreover, dynamic NMR measurement of the mesityl-substituted derivative yielded a barrier to helical inversion of 84 kJ mol-1. The optical properties and crystal packing of the cyclized products are also reported.

Superelectrophilic Activation of Phosphacoumarins towards Weak Nucleophiles via Brønsted Acid Assisted Brønsted Acid Catalysis.

The electrophilic activation of various substrates via double or even triple protonation in superacidic media enables reactions with extremely weak nucleophiles. Despite the significant progress in this area, the utility of organophosphorus compounds as superelectrophiles still remains limited. Additionally, the most common superacids require a special care due to their high toxicity, exceptional corrosiveness and moisture sensitivity. Herein, we report the first successful application of the "Brønsted acid assisted Brønsted acid" concept for the superelectrophilic activation of 2-hydroxybenzo[e][1,2]oxaphosphinine 2-oxides (phosphacoumarins). The pivotal role is attributed to the tendency of the phosphoryl moiety to form hydrogen-bonded complexes, which enables the formation of dicationic species and increases the electrophilicity of the phosphacoumarin. This unmasks the reactivity of phosphacoumarins towards non-activated aromatics, while requiring only relatively non-benign trifluoroacetic acid as the reaction medium.

Phenanthroline-Mediated Photoelectrical Enhancement in Calix[4]arene-Functionalized Titanium-Oxo Clusters.

Incorporating two organic ligands with different functionalities into a titanium-oxo cluster entity simultaneously can endow the material with their respective properties and provide synergistic performance enhancement, which is of great significance for enriching the structure and properties of titanium-oxo clusters (TOCs). However, the synthesis of such TOCs is highly challenging. In this work, we successfully synthesized a TBC4A-functionalized TOC, [Ti2(TBC4A)2(MeO)2] (Ti2; MeOH = methanol, TBC4A = tert-butylcalix[4]arene). By adjusting the solvent system, we successfully introduced 1,10-phenanthroline (Phen) and prepared TBC4A and Phen co-protected [Ti2(TBC4A)2(Phen)2] (Ti2-Phen). Moreover, when Phen was replaced with bulky 4,7-diphenyl-1,10-phenanthroline (Bphen), [Ti2(TBC4A)2(Bphen)2] (Ti2-Bphen), which is isostructural with Ti2-Phen, was obtained, demonstrating the generality of the synthetic method. Remarkably, Ti2-Phen demonstrates good stability and stronger light absorption, as well as superior photoelectric performance compared to Ti2. Density functional theory (DFT) calculations reveal that there exists ligand-to-core charge transfer (LCCT) in Ti2, while an unusual ligand-to-ligand charge transfer (LLCT) is present in Ti2-Phen, accompanied by partial LCCT. Therefore, the superior light absorption and photoelectric properties of Ti2-Phen are attributed to the existence of the unusual LLCT phenomenon. This study not only deeply explores the influence of Phen on the performance of the material but also provides a reference for the preparation of materials with excellent photoelectric performance.

Copper-Catalyzed Dearomative 1,2-Hydroamination.

Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over the last two decades, the formal hydroamination of nonactivated aromatic compounds remains an unsolved challenge. Herein, we report the extension of olefin hydroamination to aromatic π-systems by using arenophile-mediated dearomatization and Cu-catalysis to perform 1,2-hydroamination on nonactivated arenes. This strategy was applied to a variety of substituted arenes and heteroarenes to provide general access to structurally complex amines. We conducted DFT calculations to inform mechanistic understanding and rationalize unexpected selectivity trends. Furthermore, we developed a practical, scalable desymmetrization to deliver enantioenriched dearomatized products and enable downstream synthetic applications. We ultimately used this dearomative strategy to efficiently synthesize a collection of densely functionalized small molecules.

Umpolung-Enabled Divergent Dearomative Carbonylations.

Although dearomative functionalizations enable the direct conversion of flat aromatics into precious three-dimensional architectures, the case for simple arenes remains largely underdeveloped owing to the high aromatic stabilization energy. We herein report a dearomative sequential addition of two nucleophiles to arene π-bonds through umpolung of chromium-arene complexes. This mode enables divergent dearomative carbonylation reactions of benzene derivatives by tolerating various nucleophiles in combination with alcohols or amines under CO-gas-free conditions, thus providing modular access to functionalized esters or amides. The tunable synthesis of 1,3- or 1,4-cyclohexadienes as well as the construction of carbon quaternary centers further highlight the versatility of this dearomatization. Diverse late-stage modifications and derivatizations towards synthetically challenging and bioactive molecules reveal the synthetic utility. A possible mechanism was proposed based on control experiments and intermediate tracking.

Synthesis, Structures and Properties of Trioxa[9]circulene and Diepoxycyclononatrinaphthalene.

This article presents trioxa[9]circulene (3) as a novel member of hetero[n]circulenes. Its synthesis began with the synthesis of dimethoxydioxa[8]helicene (5) and used dimethoxydiepoxycyclononatrinaphthalene (4) as a key intermediate, despite the condensation reaction predominantly yielding a 1,4-addition byproduct. The structures and properties of 3-5 were extensively investigated using experimental and computational methods. Analysis of the crystal structures reveal elongation of the internal C-C bonds in the nine-membered ring of 3 compared to 4 and 5. Computational studies demonstrate the remarkable flexibility of trioxa[9]circulene's saddle-shaped polycyclic framework, while the other two compounds are rigid with large racemization barriers. Optically pure forms of 4 and 5 exhibit absorption and luminescence dissymmetry factors on the order of 10-2, with smaller values observed for compound 4. In the crystal structures, molecules of 3 stack to form columns with remarkable π-π overlap, and the π-π interactions of 4 exhibit short intermolecular C-to-C contacts. Consequently, the solution-processed film of 4 functioned as a p-type organic semiconductor in field effect transistors.

Helicene Aromaticity Deviates from the Clar Rule-On the Electronic Dissimilarity of Large Isomeric Fibonacenes.

This combined experimental and theoretical study illustrates the profound consequences of non-planarity on the electronic properties of polycyclic arenes. Three isomeric [10]fibonacene tetraesters were synthesized through a robust and regiocontrolled Perkin/Mallory approach: a nearly planar [10]phenacene derivative, a moderately twisted [10]semicircle derivative, and a 3D non-planar [10]helicene derivative. The photophysical properties of the 3D [10]helicene isomer were found to be dramatically different from the comparable ones of the [10]phenacene and [10]semicircle isomers. The aromatic properties of the [10]phenacene and [10]semicircle isomers conform well with their predictive Kekulé and Clar analyses, but the [10]helicene isomer deviates from these general topological rules, which appears to be a general phenomenon for [n]fibonacenes with n≥9.

Friedel-Crafts Acylation for Accessing Multi-Bridge-Functionalized Large Pillar[n]arenes.

Pillar[n]arenes can be constructed using a Friedel-Crafts alkylation process. However, due to the reversible nature of the alkylation, mixture of large pillar[n]arenes (n≥7) are obtained as minor products, and thus laborious purification are necessary to isolate the larger pillar[n]arenes. Moreover, inert methylene bridges are introduced during the alkylation process, and the multi-functionalization of the bridges has never been investigated. Herein, an irreversible Friedel-Crafts acylation is used to prepare pillar[n]arenes. Due to the irreversible nature of the acylation, the reaction of precursors bearing carboxylic acids and electron-rich arene rings results in a size-exclusive formation of pillar[n]arenes, in which the ring-size is determined by the precursor length. Because of this size-selective formation, laborious separation of undesired macrocycles is not necessary. Moreover, the bridges of pillar[n]arenes are selectively installed with reactive carbonyl groups using the acylation method, whose positions are determined by the precursor used. The carbonyl bridges can be easily converted into versatile functional groups, leading to various laterally modified pillar[n]arenes, which cannot be accessed by the alkylation strategy.

Rim-Based Binding of Perfluorinated Acids to Pillararenes Purifies Water.

Per- and polyfluoroalkyl substances (PFAS) pose a rapidly increasing global problem as their widespread use and high stability lead worldwide to water contamination, with significant detrimental health effects.[1] Supramolecular chemistry has been invoked to develop materials geared towards the specific capture of PFAS from water,[2] to reduce the concentration below advisory safety limits (e.g., 70 ng/L for the sum of perfluorooctane sulfonic acid, PFOS and perfluorooctanoic acid, PFOA). Scale-up and use in natural waters with high PFAS concentrations has hitherto posed a problem. Here we report a new type of host-guest interaction between deca-ammonium-functionalized pillar[5]arenes (DAF-P5s) and perfluoroalkyl acids. DAF-P5 complexes show an unprecedented 1 : 10 stoichiometry, as confirmed by isothermal calorimetry and X-ray crystallographic studies, and high binding constants (up to 106 M-1) to various polyfluoroalkyl acids. In addition, non-fluorinated acids do not hamper this process significantly. Immobilization of DAF-P5s allows a simple single-time filtration of PFAS-contaminated water to reduce the PFOS/PFOA concentration 106 times to 15-50 ng/L level. The effective and fast (<5 min) orthogonal binding to organic molecules without involvement of fluorinated supramolecular hosts, high breakthrough capacity (90 mg/g), and robust performance (>10 regeneration cycles without decrease in performance) set a new benchmark in PFAS-absorbing materials.

Catalytic Enantioselective Synthesis of Inherently Chiral Calix[4]arenes via Sequential Povarov Reaction and Aromatizations.

Inherently chiral calix[4]arenes represent a unique type of chiral molecules with significant applications, yet their catalytic enantioselective synthesis remains largely underexplored. We report herein the catalytic enantioselective synthesis of inherently chiral calix[4]arenes through the sequential organocatalyzed enantioselective Povarov reaction and aromatizations. The chiral phosphoric acid catalyzed three-component Povarov reaction involving amino group-substituted calix[4]arenes, aldehydes and (di)enamides desymmetrized the prochiral calix[4]arene substrates, which was followed by various aromatization methods, resulting in a diverse array of novel quinoline-containing calix[4]arenes with good yields and high enantioselectivities (up to 75% yield, 99% ee). The large-scale enantioselective synthesis and diverse derivatizations of the chiral calix[4]arene products highlight the value of this method. Furthermore, preliminary exploration into their photophysical and chiroptical properties demonstrate the potential applications of these novel calix[4]arene molecules.

Catalytic Enantioselective Friedel-Crafts Allenylation.

The first enantioselective Friedel-Crafts (FC) allenylation reaction for the creation of central chirality is developed under cooperative Ir(I)/(phosphoramidite,olefin) and Lewis acid catalysis. This enantioconvergent reaction utilizes racemic allenylic alcohol as the electrophile and shows compatibility with a variety of electron-rich arenes and heteroarenes. The resulting highly enantioenriched (up to >99.5:0.5 e.r.) 1,1-disubstituted allenylic methanes, bearing a benzylic carbon stereocenter, are obtained with complete regiocontrol - both on (hetero)arenes as well as on the allenylic fragment. This protocol allows for the enantioselective formal introduction of a 4-carbon alkyl chain into (hetero)arenes, along with the creation of a benzylic stereocenter. Judicious synthetic elaborations not only lead to formal enantioselective FC alkylation products of less electron-rich arenes but also of substituted arenes in ortho- and even meta-selective fashion. An intramolecular version of this FC allenylation is shown to proceed with promising enantioselectivity under the same catalytic conditions. Mechanistic studies revealed the involvement of dynamic kinetic asymmetric transformation (DyKAT) of racemic allenylic alcohols in this reaction.

Self-Inclusion Complexation of Electron-Accepting Guest into Electron-Donating Cyclic Host by Photoexcitation.

Self-inclusion complexes consisting of host-guest conjugates are one of the unique supramolecular structures because they form in-state and out-state depending on the external stimuli. Despite many reports of the stimuli-responsive self-inclusion complex formation, study of the structural relaxation from out-state to in-state by photoexcitation has been unexplored. Herein, we report that an electron-donating host and an electron-accepting guest conjugate exhibits the structural relaxation from out-state to in-state by photoexcitation. Formation of the in-state in the excited state resulted in exciplex emission along with the locally excited emission from the out-state. Moreover, this structural relaxation by photoexcitation was suppressed not only by temperature, but also by the presence of guest molecules, resulting in changes in the ratio of the dual emission intensities.

Organocatalytic Enantioselective Synthesis of Inherently Chiral Calix[4]arenes.

Inherently chiral calix[4]arenes are an excellent structural scaffold for enantioselective synthesis, chiral recognition, sensing, and circularly polarized luminescence. However, their catalytic enantioselective synthesis remains challenging. Herein, we report an efficient synthesis of inherently chiral calix[4]arene derivatives via cascade enantioselective cyclization and oxidation reactions. The three-component reaction features a broad substrate scope (33 examples), high efficiency (up to 90 % yield), and excellent enantioselectivity (>95 % ee on average). The potential applications of calix[4]arene derivatives are highlighted by their synthetic transformation and a detailed investigation of their photophysical and chiroptical properties.

Phenyl-Extended Resorcin[4]arenes: Synthesis and Highly Efficient Iodine Adsorption.

The continuous exploration of new analogs of calixarenes and pillararenes unlocks infinite opportunities in supramolecular chemistry and materials. In this work, we introduce a new class of macrocycle, phenyl-extended resorcin[4]arenes (ExR4), a unique and innovative design that incorporates unsubstituted phenylene moieties into the resorcin[4]arene scaffold. Single-crystal analysis reveals a chair-like conformation for per-methylated ExR4 (Me-ExR4) and a twisted "figure-of-eight" shaped conformation for per-hydroxylated ExR4 (OH-ExR4). Notably, OH-ExR4 demonstrates exceptional adsorption capability toward I3- ions in an aqueous solution, with a rapid kinetic rate of 1.18×10-2 g·mg-1·min-1. Furthermore, OH-ExR4 shows excellent recyclability and potential as a stationary phase in column setups. The discovery of ExR4 opens up new avenues for constructing new macrocycles and inspires further research in functional adsorption materials for water pollutant removal.

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments.

The "precursor approach" has proved particularly valuable for the preparation of insoluble and unstable π-conjugated polycyclic compounds (π-CPCs), which cannot be synthesized via in-solution organic chemistry, for their improved processing, as well as for their electronic investigation both at the material and single-molecule scales. This method relies on the synthesis and processing of soluble and stable direct precursors of the target π-CPCs, followed by their final conversion in situ, triggered by thermal activation, photoirradiation or redox control. Beside well-established reactions involving the elimination of carbon-based small molecules, i.e., retro-Diels-Alder and decarbonylation processes, the late-stage extrusion of chalcogen fragments has emerged as a highly promising synthetic tool to access a wider variety of π-conjugated polycyclic structures and thus to expand the potentialities of the "precursor approach" for further improvements of molecular materials' performances. This review gives an overview of synthetic strategies towards π-CPCs involving the ultimate elimination of chalcogen fragments upon thermal activation, photoirradiation and electron exchange.