Organocatalytic Strategies for the Synthesis of Cyclopenta‐Fused Arenes and Heteroarenes

Cyclopentanoids are omnipresent in natural products and pharmaceutically relevant compounds. Among them, cyclopenta‐fused arenes and heteroarenes possess impressive biological properties and play significant role in materials science. Consequently, several notable methods have been developed for their synthesis over the years. In this review, we mainly described metal‐free and organocatalytic approaches that led to the construction of pentannulated arenes and heteroarenes.     

Palladium‐Catalyzed Dearomative syn‐1,4‐Oxyamination

A palladium‐catalyzed dearomative syn‐1,4‐oxyamination protocol using non‐activated arenes has been developed. This one‐pot procedure utilizes arenophile chemistry, and the corresponding para‐cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access to syn‐1,4‐oxyaminated products. The reaction conditions permit a range of arenes, as well as different O‐nucleophiles, such as oximes and benzyl alcohols. Moreover, this process was established in an asymmetric fashion, delivering products with high enantioselectivity. The dearomatized products are amenable to a multitude of further derivatizations ranging from olefin chemistry to C?H activation, giving rise to a diverse set of new functionalities. Overall, this dearomative functionalization offers rapid and controlled formation of molecular complexity, enabling straightforward access to functionalized small molecules from simple and readily available arenes.     

Copper‐Promoted Conversion of Aromatic Amines into Trifluoromethylated Arenes: One‐Pot Sandmeyer Trifluoromethylation

A simple copper‐promoted one‐pot Sandmeyer trifluoromethylation of aromatic amines with Langlois’ reagent has been demonstrated. The reaction is performed in mild reaction conditions under an air atmosphere with good substrate scope and functional group compatibility. It provides an alternative and straightforward synthetic approach to access a variety of trifluoromethylated arenes.     

[3+2]‐Cycloaddition for Fully Decorated Vinyl‐1,2,3‐Triazoles: Design,Synthesis and Applications

The s mall heterocyclic ring of the 1,2,3‐triazole module is one of the most widely investigated compounds in numerous applications of biological, medicinal, pharmaceutical and materially important molecules. In this regard, a large number of synthetic methodologies and approaches have already been reported to construct such a heterocyclic core structure in a selective manner. However, the vinyl‐substituted 1,2,3‐triazole moiety is another privileged segment in heterocyclic chemistry. The selective introduction of simple vinyl and functionalized vinyl groups onto the three different positions of the 1,2,3‐triazole framework can significantly improve the properties of the molecule. Accordingly, high‐yielding efficient approaches for the selective construction of vinyl‐containing 1,2,3‐triazoles becomes a promising branch of chemistry among practitioners of industry and academia. In this minireview, we have discussed recent advances in the construction of highly selective three different vinyl‐containing 1,2,3‐triazoles. In addition, representative synthetic methodologies and approaches for the corresponding three different classes of vinyl‐1,2,3‐triazoles and their applications have been described as well in this review.     

Efficient Synthesis of Sterically Hindered Arenes Bearing Acyclic Secondary Alkyl Groups by Suzuki–Miyaura Cross‐Couplings

Bulky P,P?O ligands were designed to inhibit isomerization and reduction side reactions during the cross coupling between sterically hindered aryl halides and alkylboronic acids. Suzuki–Miyaura cross‐couplings between di‐ortho‐substituted aryl bromides and acyclic secondary alkylboronic acids have been achieved with high yields. The method has also enabled the preparation of ortho‐alkoxy di‐ortho‐substituted arenes bearing isopropyl groups in excellent yields. The utility of the synthetic method has been demonstrated in a late‐stage modification of estrone and in the application to a new synthetic route toward gossypol.     

Catalyst‐Free Polyhydroboration of Dodecaborate Yields Highly Photoluminescent Ionic Polyarylated Clusters

The incorporation of polyhedral boranes into novel photoluminescent materials is an area with increasing interest. While the neutral carboranes have been widely investigated for this purpose, the dodecaborate ion has received much less attention. Herein we report a significant expansion to the scope of substitution reactions for the dodecaborate ion, whereby this cluster was observed to react directly with a wide range of arenes in a step‐wise and controlled manner. In the products of these reactions, the dodecaborate ion serves as a core upon which up to nine mono‐ or polycyclic aromatic hydrocarbon ligands are exohedrally bonded. Spectroscopic evidence suggests the presence of conjugation between the π systems of the aryl ligands and the dodecaborate core, resulting in materials which exhibit high solution‐phase photoluminescence, as well as molar absorptivities and Stokes shifts that are significantly larger than those of the free arenes from which they were derived. We propose that this broad reactivity is a valuable synthetic tool for the incorporation of polyhedral boron into novel organic structures.     

Arenophile‐Mediated Dearomative Reduction

A dearomative reduction of simple arenes has been developed which employs a visible‐light‐mediated cycloaddition of arenes with an N‐N‐arenophile and in situ diimide reduction. Subsequent cycloreversion or fragmentation of the arenophile moiety affords 1,3‐cyclohexadienes or 1,4‐diaminocyclohex‐2‐enes, compounds that are not synthetically accessible using existing dearomatization reactions. Importantly, this strategy also provides numerous opportunities for further derivatization as well as site‐selective functionalization of polynuclear arenes.     

Prismarene: An Emerging Naphthol‐Based Macrocyclic Arene

Phenol‐based macrocyclic arenes have been widely used in supramolecular chemistry, significantly enriching the toolbox of the field. In contrast, naphthol‐based macrocyclic arenes are rather underdeveloped. Very recently, Gaeta and co‐workers successfully synthesized such macrocycles (referred to as prism[n]arenes) with good guest‐binding ability by reacting 2,6‐dimethoxynaphthalene with paraformaldehyde under optimized conditions. In view of the simple synthesis and good host–guest chemistry, we anticipate that this macrocycle will find similar success and wide applications as the phenol‐based macrocyclic arenes.     

Synthesis,Structure, and Reactivity of 5‐(Aryl)dibenzothiophenium Triflates

A synthetic protocol for the preparation of 5‐(aryl)dibenzothiophenium salts starting from inexpensive dibenzothiophene S‐oxide and simple arenes is reported. The scope of the method regarding the nature of the arene is evaluated, intermediates along the reaction sequence have been trapped, and side‐reactions identified. In addition, the X‐ray structures of a complete set of these salts are reported and their reactivities studied. Specifically, chemoselective Suzuki coupling is observed at the dibenzothiophenium in the presence of iodides.     

N‐Arylation of Diketopyrrolopyrroles with Aryl Triflates

A new methodology for the double N‐arylation of diketopyrrolopyrroles with aryl triflates has been developed. It is now possible to prepare diketopyrrolopyrroles bearing N‐substituents derived from naphthalene, anthracene and coumarin in two steps from commercially available phenols. This represents the first time arenes lacking strong electron‐withdrawing groups were inserted onto lactamic nitrogen atoms via arylation. The ability to incorporate heretofore unprecedented substituents translates to increased modulation of the resulting photophysical properties such as switching‐on/off solvatofluorochromism. TD‐DFT calculations have been performed to explore the nature of the relevant excited states. This new synthetic method made it possible to elucidate the influence of such substituents on the absorption and emission properties of tetraaryl substituted diketopyrrolopyrroles.     

Heteroatom‐Free Arene‐Cobalt and Arene‐Iron Catalysts for Hydrogenations

75 years after the discovery of hydroformylation, cobalt catalysts are now undergoing a renaissance in hydrogenation reactions. We have evaluated arene metalates in which the low‐valent metal species is—conceptually different from heteroatom‐based ligands—stabilized by π coordination to hydrocarbons. Potassium bis(anthracene)cobaltate 1 and ‐ferrate 2 can be viewed as synthetic precursors of quasi‐“naked” anionic metal species; their aggregation is effectively impeded by (labile) coordination to the various π acceptors present in the hydrogenation reactions of unsaturated molecules (alkenes, arenes, carbonyl compounds). Kinetic studies, NMR spectroscopy, and poisoning studies of alkene hydrogenations support the formation of a homogeneous catalyst derived from 1 which is stabilized by the coordination of alkenes. This catalyst concept complements the use of complexes with heteroatom donor ligands for reductive processes.     

Ortho‐Stabilized 18F‐Azido Click Agents and their Application in PET Imaging with Single‐Stranded DNA Aptamers

Azido ¹⁸F‐arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition (“click chemistry”) for positron emission tomography (PET). However, routine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches. A high‐yielding direct radiofluorination for azido ¹⁸F‐arenes was achieved through the development of an ortho‐oxygen‐stabilized iodonium derivative (OID). This OID strategy addresses an unmet need for a reliable azido ¹⁸F‐arene clickable agent for bioconjugation reactions. A ssDNA aptamer was radiolabeled with this agent and visualized in a xenograft mouse model of human colon cancer by PET, which demonstrates that this OID approach is a convenient and highly efficient way of labeling and tracking biomolecules.     

Directed meta‐Selective Bromination of Arenes with Ruthenium Catalysts

A Ru‐catalyzed direct C? H activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through radical‐mediated bromination when NBS is utilized as the bromine source. This type of transformation has opened up a new direction for the radical non‐ipso functionalization of metal with regard to future C? H activation development that would allow the remote functionalization of aromatic systems.     

Palladium‐Catalyzed Dearomative syn‐1,4‐Carboamination with Grignard Reagents

A protocol for palladium‐catalyzed dearomative functionalization of simple, nonactivated arenes with Grignard reagents has been established. This one‐pot method features a visible‐light‐mediated [4+2] cycloaddition between an arene and an arenophile, and subsequent palladium‐catalyzed allylic substitution of the resulting cycloadduct with a Grignard reagent. A variety of arenes and Grignard reagents can participate in this process, forming carboaminated products with exclusive syn‐1,4‐selectivity. Moreover, the dearomatized products are amenable to further elaborations, providing functionalized alicyclic motifs and pharmacophores. For example, naphthalene was converted into sertraline, one of the most prescribed antidepressants, in only four operations. Finally, this process could also be conducted in an enantioselective fashion, as demonstrated with the desymmetrization of naphthalene.     

Controlled Self‐Assembly by Mono‐p‐sulfonatocalix[n]arenes and Bis‐p‐sulfonatocalix[n]arenes

The complexation‐induced critical aggregation concentrations of 1‐pyrenemethylaminium by mono‐p‐sulfonatocalix[n]arenes and bis‐p‐sulfonatocalix[n]arenes (n=4, 5) were systemically measured by fluorescence spectroscopy. In all cases, the complexation‐induced critical aggregation concentration decreases by about 3 times upon addition of p‐sulfonatocalix[n]arenes. However, the optimal molar ratios for the aggregation of 1‐pyrenemethylaminium by mono‐p‐sulfonatocalix[n]arenes and bis‐p‐sulfonatocalix[n]arenes are distinctly different: For mono‐p‐sulfonatocalix[n]arenes, the optimum mixing ratio for the aggregation of 1‐pyrenemethylaminium is 1:4 mono‐p‐sulfonatocalix[n]arenes/1‐pyrenemethylaminium, whereas only 2.5 molecules of 1‐pyrenemethylaminium can be bound by one cavity of bis‐p‐sulfonatocalix[n]arenes. The intermolecular complexation of mono‐p‐sulfonatocalix[n]arenes and bis‐p‐sulfonatocalix[n]arenes with 1‐pyrenemethylaminium led to the formation of two distinctly different nanoarchitectures, which were shown to be nanoscale vesicle and rod aggregates, respectively, by using dynamic laser scattering, TEM, and SEM. This behavior is also different from the fiber‐like aggregates with lengths of several micrometers that were formed by 1‐pyrenemethylaminium itself above its critical aggregation concentration. Furthermore, the obtained nanoaggregates exhibit benign water solubility, self‐labeled fluorescence, and, more importantly, temperature responsiveness.     

Nickel‐Catalyzed Difluoroalkylation of (Hetero)Arylborons with Unactivated 1‐Bromo‐1,1‐difluoroalkanes

A nickel‐catalyzed cross‐coupling between (hetero)arylborons and unactivated 1‐bromo‐1,1‐difluoroalkanes has been developed. The use of two ligands (a bidentate bipyridine‐based ligand, 4,4′‐ditBu‐bpy, and a monodentate pyridine‐based ligand, DMAP) offers a highly efficient nickel‐based catalytic system to prepare difluoroalkylated arenes which have important applications in medicinal chemistry.     

Aromatic Homologation by Non‐Chelate‐Assisted RhIII‐Catalyzed CH Functionalization of Arenes with Alkynes

Larger condensed arenes are of interest owing to their electro‐ and photochemical properties. An efficient synthesis is the catalyzed aromatic annulation of a smaller arene with two alkyne molecules. Besides difunctionalized starting materials, directed C? H functionalization can be used for such aromatic homologation. However, thus far the requirement of either pre‐functionalized substrates or suitable directing groups were limiting this approach. Herein, we describe a rhodium(III)‐catalyzed method allowing the use of completely unbiased arenes and internal alkynes. The reaction works best with copper(II) 2‐ethylhexanoate and decabromodiphenyl ether as the oxidant combination. This aromatic annulation tolerates a variety of functional groups and delivers homologated condensed arenes. Aside from simple benzenes, naphthalenes and higher condensed arenes provide access to highly substituted and highly soluble acenes structures having important electronic and photophysical properties.     

Carbon Dots: Bottom‐Up Syntheses,Properties, and Light‐Harvesting Applications

The development of cost‐effective and environmentally friendly photocatalysts and photosensitizers has received tremendous attention because of their potential utilization in solar‐light‐harvesting applications. In this respect, carbon dots (CDs) prepared by bottom‐up methods have been considered to be promising light‐harvesting materials. Through their preparation from various molecular precursors and synthetic methods, CDs exhibit excellent optical and charge‐transfer properties. Furthermore, their photophysical properties can be readily optimized and enhanced by means of doping, functionalization, and post‐synthetic treatment. In this review, we summarize the recent progress in CDs synthesized using bottom‐up approaches. These CDs exhibit strong light absorption and unique electron donor/acceptor capabilities for light‐harvesting applications. We anticipate that this review will provide new insights into novel types of photosensitizers and photocatalysts for a wide range of applications.     

Nickel‐Catalyzed Reductive Coupling for Transforming Unactivated Aryl Electrophiles into β‐Fluoroethylarenes

We report herein a facile synthetic method for converting unactivated (hetero)aryl electrophiles into β‐fluoroethylated (hetero)arenes via nickel‐catalyzed reductive cross‐couplings. This coupling reaction features the involvement of FCH₂CH₂ radical intermediate rather than β‐fluoroethyl manganese species which provides effective solutions to the problematic β‐fluoride side eliminations. The practical value of this protocol is further demonstrated by the late‐stage modification of several complex ArCl or ArOH‐derived bioactive molecules.     

Silver‐Promoted Oxidative Benzylic C−H Trifluoromethoxylation

A silver‐promoted oxidative benzylic C?H trifluoromethoxylation has been reported for the first time. With trifluoromethyl arylsulfonate as the trifluoromethoxylation reagent, various arenes, having diverse functional groups, undergo trifluoromethoxylation of their benzylic C?H bonds to form trifluoromethyl ethers under mild reaction conditions. In addition, the trifluoromethoxylation and the fluorination of methyl groups of electron‐rich arenes have been achieved to prepare α‐fluorobenzyl trifluoromethyl ethers in one step.