Direct Arylation Research Articles

Direct Arylation Polycondensation of β-Fluorinated Bithiophenes to Polythiophenes: Effect of Side Chains in C–Br Monomers

Six polythiophenes (PThs) were synthesized via direct arylation polycondensation (DArP) with β-fluorinated bithiophenes, that is, 4,4′-difluoro-2,2′-bithiophene (2FBT) and 3,3′,4,4′-tetrafluoro-2,2′-bithiophene (4FBT), as the C–H monomers and 5,5′-dibromo-2,2′-bithiophenes DCBT-2Br, DABT-2Br, and DTBT-2Br that carry alkoxycarbonyl, alkyl, and alkylthienyl side chains at 4,4′-positions, respectively, as the C–Br monomers. Both 2FBT and 4FBT are highly reactive for DArP, and high molecular weight PThs with unobservable chain defects were successfully synthesized from 2FBT/DCBT-2Br, 2FBT/DABT-2Br, 2FBT/DTBT-2Br, and 4FBT/DTBT-2Br. However, the DArP of 4FBT with DCBT-2Br and DABT-2Br produced PThs containing C–H/C–H homo-coupling defects along with relatively lower molecular weights. Detailed theoretical analysis suggests that the occurrence of C–Br reduction-provoked C–H/C–H homo-coupling for 4FBT/DCBT-2Br and 4FBT/DABT-2Br monomer pairs originated from the poor selectivity between the cis- and trans-forms of transition states in the concerted metalation–deprotonation (CMD) process is responsible for the formation of structural defects and depressed molecular weights. This research reveals that a C–H monomer with high reactivity and selectivity is not sufficient for the synthesis of well-defined conjugated polymers via DArP, and the structure of the C–Br monomer also has a significant impact on the results of DArP via influencing the catalytic cycles.

Benzimidazole-based N[sbnd]heterocyclic carbene ruthenium(II) complexes: Synthesis and C[sbnd]H bond activation properties

The transition-metal-promoted CH activation has become an efficient as well as an atom-economic methodology for the synthesis of a wide array of organic molecules. Herein, the reaction of RuCl2(p-cymene)]2 with 1,3-dialkylbenzimidazolium salts (1a-c) in the presence of a small excess of cesium carbonate yields chelated η6-arene, η1-carbene ruthenium complexes (2a-c). All synthesized compounds were characterized by elemental analysis and NMR spectroscopy. The catalytic activity of [Cl2Ru(η6-arene, η1-carbene)] complexes (2a-c) were evaluated in the direct arylation of 2-phenylpyridine and 1-phenylpyrazole with (hetero)aryl chlorides derivative.

Facile Direct C-H Arylation Polymerization of Conjugated Polymer, PDCBT, for Organic Solar Cells.

Direct arylation polymerization (DArP) is a synthetic method for conjugated polymers; in DArP, organometallic functionalization steps are omitted and there are no toxic byproducts. As a result, it is considered a more sustainable alternative compared to conventional methods such as Stille polymerization. To explore the possibility of DArP-based polymers as donor materials in organic solar cells (OSCs), a series of conjugated polymers based on the structure of PDCBT (poly[2,2''''-bis[[(2-butyloctyl)oxy]carbonyl][2,2':5',2'':5'',2'''-quaterthiophene]-5,5'''-diyl]) are synthesized using DArP and Stille polymerization. By controlling the monomer concentration and reaction time in DArP, DArP-5 with the highest Mn (21.9 kDa) can be obtained and its optoelectronic properties, electrochemical properties, and microscopic molecular ordering are comparable to those of Stille-based PDCBT (Stille-P). Analysis of the polymer structure indicates no structural defects such as crosslinking from undesired β-coupling reactions in DArP-5. Upon blending with the PC71 BM acceptor molecule, an increase in the crystallite size of DArP-5 is also observed. In OSCdevices with a polymer:PC71 BM bulk-heterojunction photoactive layer, DArP-5 demonstrates a comparable power conversion efficiency of 5.8% with that of Stille-P (5.5%). These results prove that DArP is suitable for synthesizing PDCBT, and DArP-based PDCBT can be used in OSCs as an alternative of Stille-based one.

An improved greener process for the direct C[sbnd]H:C[sbnd]H arylation polymerization of 3,4-Propylenedioxythiophene derivatives

In this manuscript, we report an improved method for the direct CH:CH arylation process for the polymerization of 3,4-propylenedioxythiophene (Pro-DOT) derivatives. As an alternative to traditional oxidative direct arylation (DAH) polymerization process, the direct CH:CH arylation method has emerged as promising method to polymerize activated aromatic systems. Herein, we report a significant improvement to existing CH:CH arylation polymerization of Pro-DOT derivatives wherein molecular oxygen was used as oxidizing agent to replace the commonly used inorganic oxidants. Furthermore, use of molecular oxygen enabled us to carry out the polymerization without any ancillary ligands. This makes the whole process greener and economically more attractable. The process was optimized by measuring the rate of conversion of monomer using HPLC. It was surprising to note that there is a trade-off between the rate of polymerization and percentage conversion. The final optimum temperature was found to be 70 °C. Therefore, the polymerization was initially carried out at 70 °C till the complete conversion of monomer followed by at higher temperature to build the molecular weight. This stepwise ramping of temperature allowed us to get polymer with 72 % yield and a weight average molecular weight of 44 kDa. The final purified polymers were characterized by GPC, 1H NMR and UV–vis studies.

Supported Eosin Y as a Photocatalyst for C-H Arylation of Furan in Batch and Flow.

Eosin Y is one of the most popular organic dyes used as a photoredox catalyst and is largely employed in photochemical reactions both as a homogeneous and heterogeneous photocatalyst after immobilization. Immobilization of Eosin Y onto a solid support has many advantages, such as the possibility of recovery and reuse of the photocatalyst and the possibility of its use under flow conditions. In this paper, we report our findings on the immobilization of Eosin Y onto Merrifield resin and its application in the direct photochemical arylation of furan with aryldiazonium salts. The synthesized supported photocatalyst was used in batch reactions under heterogeneous conditions with different aryl diazonium salts, and its recovery and recycle were demonstrated for up to three times. The immobilized photocatalyst was then loaded in a packed-bed reactor and used under continuous flow conditions. The flow reaction allowed the arylated products to be obtained with higher productivity and space-time-yield than the batch in a very short reaction time.

Visible Light Photoredox-Catalyzed Direct C-H Arylation of Quinoxalin-2(1H)-ones with Diaryliodonium Salts.

A photoredox-catalyzed direct arylation of quinoxalin-2-(1H)-ones using diaryliodonium triflates as the convenient, stable, and cheap aryl source is described. A broad variety of quinoxalin-2-(1H)-ones are shown to react with structurally and electronically diverse diaryliodonium triflates, allowing efficient access to a wide variety of pharmaceutically important 3-arylquinoxalin-2-(1H)-ones. The presented method is attractive with regard to operational simplicity, mild conditions, broad scope, scalability, and high functional group tolerance.

Cyclic Hypervalent Iodine-Induced Oxidative Phenol and Aniline Couplings with Phenothiazines

C-H/N-H bond functionalization for direct intermolecular aryl C-N couplings is a useful synthetic process. In this study, we achieved metal-free cross-dehydrogenative coupling of phenols and anilines with phenothiazines using hypervalent iodine reagents. This method affords selective amination products under mild conditions. Electron-rich phenols and anilines could be employed, affording moderate-to-high yields of N-arylphenothiazines. Aniline amination proceeded efficiently at 20 °C, a previously unreported phenomenon.

Palladium-Catalyzed Direct Synthesis and Insecticidal Activity of Arylmatrine Derivatives

Pd(OAc)2/NiXantphos efficiently catalyzed the direct arylation at the C-14 position of matrine, leading to 38 arylmatrine derivatives (1a-19a and 1b-19b) in good yields. Most of these matrine analogues showed enhanced insecticidal effects superior to the parent compound matrine. Among them, the 3,5-diphenylbenzene analogue (8b) exhibited the most potent in vivo antifeedant activity (EC50 = 0.19 mg/mL) against Spodoptera exigua (Hübner), with approximately 25-fold more activity than matrine, for which the preliminary mechanism of action was verified through enzyme inhibition activities and molecular docking. Compound 8b as well displayed in vitro antiproliferation activity on Sf9 insect cells (IC50 = 8.1 μM), and its apoptotic induction effect was illustrated by morphological observation and DNA fragment analysis. Overall, the above results provide further information on the potential of arylmatrine-type lead compounds for the prevention and control of insect pests.

Enabling Electron Injection for Microbial Electrosynthesis with n-Type Conjugated Polyelectrolytes.

Microbial electrosynthesis-using renewable electricity to stimulate microbial metabolism-holds the promise of sustainable chemical production. A key limitation hindering performance is slow electron-transfer rates at biotic-abiotic interfaces. Here a new n-type conjugated polyelectrolyte is rationally designed and synthesized and its use is demonstrated as a soft conductive material to encapsulate electroactive bacteria Shewanella oneidensis MR-1. The self-assembled 3D living biocomposite amplifies current uptake from the electrode ≈674-fold over controls with the same initial number of cells, thereby enabling continuous synthesis of succinate from fumarate. Such functionality is a result of the increased number of bacterial cells having intimate electronic communication with the electrode and a higher current uptake per cell. This is underpinned by the molecular design of the polymer to have an n-dopable conjugated backbone for facile reduction by the electrode and zwitterionic side chains for compatibility with aqueous media. Moreover, direct arylation polycondensation is employed instead of the traditional Stille polymerization to avoid non-biocompatible tin by-products. By demonstrating synergy between living cells with n-type organic semiconductor materials, these results provide new strategies for improving the performance of bioelectrosynthesis technologies.

Arylation Reactions in the Synthesis of Biologically Important 2,5-Diaryl-1,3,4-Oxadiazoles

Apart from carbon atoms, some cyclic molecules contain other elements and play an extraordinary role in human life. Among these systems, 1,3,4-oxadiazole derivatives deserve special attention due to their biological properties such as antibacterial, antifungal, antitumor, and anti-inflammatory properties. They are commonly used in pharmacology, as well as in fungicidal, herbicidal, and insecticidal agricultural applications. The 1,3,4-oxadiazole fragment is connected directly to other aromatic systems and can be found in the structure of some commercially available drugs, or in potential drug candidates in the final pharmacological testing phase. Therefore, scientists are looking for new hybrid materials based on 1,3,4-oxadiazoles and other biologically active molecules. The most popular methods for constructing new carbon–carbon bonds between two aromatic species include direct arylation, condensation, and cross-coupling reactions. This review article, comprising the literature from 2009 to 2022, discusses a number of arylation reactions in the synthesis of 2,5-diaryl-1,3,4-oxadiazole derivatives.

Development of regio-regular poly(3-hexylthiophene) by direct arylation using Fagnou's conditions.

Semiconducting polymers are widely studied due to their applications in photovoltaic devices, the predominant conjugated polymer used in organic solar cells (OSCs) is semicrystalline poly(3-hexylthiophene) P3HT, which can be produced by easy, low-cost and environmentally friendly methods such as direct arylation polymerization (DArP) (N.S. Gobalasingham et al. 2018). Due to its solution processing, deposition on different types of substrates, even flexible, with technologies such as spin coating and roll to roll, it is a feasible option for large-scale production. In this work we present the synthesis, physicochemical characterization of a regio- regular P3HT by the direct arylation method using Fagnou conditions and its evaluation on the active layer of OSCs with bulk heterojunction architecture.

A Route to Conjugated Monomers and Polymers Incorporating 2,5-Connected Oxazole in the Backbone.

Joining of imidazole, pyrimidine, and oxazole to other conjugated core units was explored in pursuit of yielding monomers to synthesize organic semiconducting polymers. Regioregular oxazole-flanked thiophene, benzothiadiazole, naphthalene diimide (NDI), and thienopyrroledione (TPD) were successfully isolated via stannylation of oxazole and the Stille coupling of brominated core units (overall yields ranging from ca. 40 to 60%). From subsequent direct arylation polymerization, NDI/oxazole/TPD-containing regioisomeric polymers were obtained with optical and electrochemical orbital energetics in the semiconducting regime.

Pd-Catalyzed Direct Deoxygenative Arylation of Non-π-Extended Benzyl Alcohols with Boronic Acids via Transient Formation of Non-Innocent Isoureas

We report the direct arylation of non-derivatized alcohols with boronic acids and demonstrate that a Pd catalyst, in combination with a carbodiimide, can be used to forge a C–C bond via the transient formation of non-innocent isoureas from the corresponding alcohols. Besides further polarizing the C–O bond, the transiently generated isourea contains a masked base that is released during the reaction to enable catalytic turnover under exogenous base-free conditions. The developed concept was benchmarked against the coupling of non-π-extended benzyl alcohols and boronic acids and led to the formation of a C–C bond between differently decorated coupling partners. Notably, the strategic generation of non-innocent isoureas endows this C–O cleavage reaction with high orthogonality over conventional electrophiles and enables the employment of highly base-sensitive boronic acids. Additionally, the preformed isoureas can be leveraged for rapid (5 min reaction time) exogenous base-free coupling reactions, which work under conventional thermal conditions and do not rely on customized catalysts or specialized equipment. The synthetic investigations were also complemented by preliminary mechanistic studies. More broadly, the presented work bridges a conceptual gap between two important research areas, that is, carbodiimide-mediated alcohol activation and deoxygenative transition metal-catalyzed coupling chemistry, providing a promising blueprint for direct catalytic deoxygenative reactions.

Straightforward Access to Multifunctional π-Conjugated P-Heterocycles Featuring an Internal Ylidic Bond.

We report the straightforward one‐pot synthesis of novel 5‐ or 6‐membered P‐heterocycles featuring an internal ylidic bond: P‐containing acenaphthylenes and phenanthrenes. The stability of the compounds tolerates post‐functionalization through direct arylation to introduce electron‐rich/poor substituents and the synthetic strategy is also compatible with the preparation of more elaborate polyaromatic scaffolds such as acenes and helicenes. Using a joint experimental (X‐ray analysis, optical and redox properties) and theoretical approach, we perform a full structure–property relationships study on these new platforms. In particular, we show that molecular engineering allows not only tuning their absorption/emission across the entire visible range but also endowing them with chiroptical or non‐linear optical properties, making them valuable dyes for a large panel of photonic or opto‐electronic applications.

Straightforward Access to Multifunctional π‐Conjugated P‐Heterocycles Featuring an Internal Ylidic Bond**

AbstractWe report the straightforward one‐pot synthesis of novel 5‐ or 6‐membered P‐heterocycles featuring an internal ylidic bond: P‐containing acenaphthylenes and phenanthrenes. The stability of the compounds tolerates post‐functionalization through direct arylation to introduce electron‐rich/poor substituents and the synthetic strategy is also compatible with the preparation of more elaborate polyaromatic scaffolds such as acenes and helicenes. Using a joint experimental (X‐ray analysis, optical and redox properties) and theoretical approach, we perform a full structure–property relationships study on these new platforms. In particular, we show that molecular engineering allows not only tuning their absorption/emission across the entire visible range but also endowing them with chiroptical or non‐linear optical properties, making them valuable dyes for a large panel of photonic or opto‐electronic applications.

Palladium-catalyzed direct C5-arylation or C4,C5-diarylation of 2-alkylisothiazol-3-ones

The regioselectivity of the Pd-catalyzed direct arylation of unsubstituted 2-alkylisothiazol-3(2H)-ones was investigated. Conditions for the regioselective palladium-catalyzed direct C5-arylation of 2-alkylisothiazol-3-ones using aryl bromides as the coupling partners are reported. This procedure tolerates a wide variety of substituents such as nitro, nitrile, ester, chloro, fluoro, trifluoromethyl, trifluoromethoxy, difluoromethoxy at para-, meta- and also ortho-positions on the aryl bromide. Both methyl- and octyl-substituents at 2-position of alkylisothiazol-3-ones are tolerated. Moreover, at a more elevated temperature in the presence of a larger excess of the aryl bromide, the access to the C4,C5-diarylated alkylisothiazol-3-ones is also possible, revealing that the C4-position of isothiazol-3(2H)-ones is reactive for direct arylation when the C5-position is blocked. Therefore, this method provides a one pot access to a wide variety of isothiazolinone derivatives allowing to modify easily their biological properties.

Photophysics and thermally-induced degradation of P2TI-DD, a polymer synthesized by direct arylation reaction

Photophysics and thermally-induced degradation of P2TI-DD, a polymer synthesized by direct arylation reaction

Total synthesis of jadomycins A, B, and l-digitoxosyl-phenanthroviridin

We report the total synthesis of jadomycins A, B, and l-digitoxosyl-phenanthroviridin. 2-Aryl-5-hydroxy-1,4-naphthoquinones, which were synthesized utilizing a Pd-catalyzed direct arylation of 5-hydroxy-1,4-naphthoquinone with aryl iodide, were converted into jadomycin A through introduction of l-isoleucine, followed by oxidative cyclization. Mitsunobu reaction of jadomycin A with 3,4-di-O-acetyl-l-digitoxose, which was prepared from commercially available 3,4-di-O-acetyl-6-deoxy-l-glucal, followed by deacetylation, gave jadomycin B. Additionally, the first total synthesis of l-digitoxosyl-phenanthroviridin was successful via Mitsunobu reaction of phenanthroviridin aglycon with 3,4-di-O-acetyl-l-digitoxose.

Diketopyrrolopyrrole and perylene diimine-based large π-molecules constructed via C–H direct arylation

Diketopyrrolopyrrole (DPP) and perylene diimine (PDI) dye moieties with unique structure and strong light absorption have been widely explored as building blocks for organic opto-electronic materials. In this work, we implement a proof-of-concept of welding DPP and PDI together as propellers for the design of novel molecules with star-shaped or three-dimensional (3D) geometries and minimized self-aggregation. Three large conjugated molecules Ph(DPP-PDI)3, Py(DPP-PDI)4 and SF(DPP-PDI)4 with different central cores, i.e., benzene, pyrene and spirofluorene, are designed and facilely synthesized via atom- and step-economic C–H direct arylation (DACH) coupling. The optical, electrochemical properties and photovoltaic performance of target molecules with varied geometries, are systematically investigated by UV–vis absorption, cyclic voltammetry and bulk heterojunction devices, which reveal that 3D molecules have a broader light absorption, much higher extinction coefficients and more favorable energy levels compared with mono DPP-PDI precursor. Our study demonstrates that DACH reaction is an effective and extensible method to prepare branched or 3D π-electronic materials, and provides a guideline for the rational design and synthesis of complex π-molecules in a simple way.

Copper‐Promoted Direct Decarboxylative C3‐Acylation of Electron‐Rich Indolizines Using α‐Keto Acids

AbstractC‐3 substituted indolizines are important biological heterocycles and luminescent molecules. The development of new methods for direct arylation of indolizines is highly desired. Herein, the C3‐acylation of electron‐rich indolizines with α‐keto acids through Cu‐promoted decarboxylation was descried. Under this simple reaction conditions, a variety of indolizine derivatives were synthesized and characterized. The structure of product 3 a was confirmed in an X‐ray crystal analysis. In addition, the mechanism was also proposed.