Eight-Membered Palladacycle Intermediate Enabled Synthesis of Cyclic Biarylphosphonates.

Transition-metal-catalyzed coupling reactions that involve the direct functionalization of insert C-H bond represent one of the most efficient strategies for forming carbon-carbon bonds. Herein, a palladium-catalyzed intramolecular C-H bond arylation of triaryl phosphates is reported to access seven-membered cyclic biarylphosphonate targets. The reaction is achieved via a unique eight-membered palladacyclic intermediate and shows good functional group compatibility. Meanwhile, the product can be readily converted into other valuable phosphate compounds.

Nonstoichiometric Direct Arylation Polymerization of Octafluorobiphenyl with 2,7-Diiodofluorene for Regulating CH Terminals of π-Conjugated Polymer.

Nonstoichiometric direct arylation polycondensation of 2,2',3,3',5,5',6,6'-octafluorobiphenyl with excess of 2,7-diiodo-9,9-dioctyl-9H-fluorene is demonstrated. Pd/Ag dual-catalyst system under water/2-methyltetrahydrofuran biphasic conditions enables direct arylation under mild conditions and promotes the intramolecular transfer of a Pd catalyst walking through the fluorene moiety. The nonstoichiometric direct arylation polycondensation under the optimized reaction conditions produces the corresponding π-conjugated polymer with a high molecular weight and terminal octafluorobiphenyl units at both ends.

Thienoisoindigo-Based Conjugated Polymers Synthesized by Direct Arylation Polycondensation.

A series of thienoisoindigo (TIG)-based conjugated polymers (CPs) with high molecular weights are synthesized by direct arylation polycondensation (DArP) by using TIG derivatives as CBr monomer and multi-halogenated thiophene derivatives, i.e., (E)-1,2-bis(3,4-difluorothien-2-yl)ethene (4FTVT), (E)-1,2-bis(3,4-dichlorothien-2-yl)ethene (4ClTVT), 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT), and 3,3',4,4'-tetrachloro-2,2'-bithiophene (4ClBT), as CH monomers. Density functional theory (DFT) calculations reveal the high selectivity between α-CH bonds in 4FTVT, 4ClTVT, 4FBT, and 4ClBT and ß-CH bonds in TIG CBr monomer. All four resulting CPs exhibit low optical bandgaps of ca. 1.20 eV and ambipolar transport characteristics with both electron and hole mobility above 0.1 cm2  V-1  s-1 as elaborated with organic thin-film transistors (OTFTs). The polymer TIG-4FTVT delivers the best device performance. With this polymer, n-channel OTFTs with electron mobility up to 1.67 cm2  V-1  s-1 and p-channel OTFTs with hole mobility up to 0.62 cm2  V-1  s-1 are fabricated by modifying source/drain electrodes with polyethylenimine ethoxylated (PEIE) and MoO3 , respectively, to selectively inject electrons and holes.

Mono or double Pd-catalyzed C-H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives.

The Pd-catalyzed annulative π-extension of 1,8-dibromonaphthalene for the preparation of fluoranthenes in a single operation has been investigated. With specific arenes such as fluorobenzenes, the Pd-catalyzed double functionalization of C-H bonds yields the desired fluoranthenes. The reaction proceeds via a palladium-catalyzed direct intermolecular arylation, followed by a direct intramolecular arylation step. As the C-H bond activation of several benzene derivatives remains very challenging, the preparation of fluoranthenes from 1,8-dibromonaphthalene via Suzuki coupling followed by intramolecular C-H activation has also been investigated to provide a complementary method. Using the most appropriate synthetic route and substrates, it is possible to introduce the desired functional groups at positions 7-10 on fluoranthenes.

Facile Synthesis of Bis-pentafluoroarylated Anthracene Derivatives for N-type Organic-Field-Effect Transistor Applications.

Diphenylanthracene (DPA) and its derivatives are promising semiconducting materials for p-type organic-field-effect transistors (OFETs). In this study, to develop n-type semiconducting materials with an anthracene core, pentafluorobenzene was introduced into anthracene by C-H direct arylation, enabling the synthesis of various bis(pentafluorophenyl)anthracene (DPA-F) derivatives. The high reactivity of the pentafluorobenzene C-H bond allows direct arylation for synthesizing DPA-F derivatives in a single step. The introduction of strong electron-withdrawing pentafluorophenyl groups provides the anthracene derivatives with n-type semiconducting properties, in contrast to the p-type properties of the parent DPAs. Among the synthesized compounds, 2,6-bis(pentafluorophenyl)anthracene shows a high electron mobility of 0.12±0.02 cm2 /Vs and an on/off ratio>106 in OFETs. The high crystallinity results in the smooth electron transport. This study provides a facile synthetic method for n-type semiconducting materials and insights into the molecular design of the positional effects of aromatic substituents on anthracene.

Tunable Regioselectivity in C-H-Activated Direct Arylation Reactions of Dithieno[3,2-b:2',3'-d]pyrroles.

In this study, regioselectively controlled direct arylation of dithieno[3,2-b:2,3'-d]pyrroles (DTPs) is reported. By carefully selecting the catalytic system, Pd source, ligand, and additives, we achieved either selective N-arylation or unprecedented ß-arylation and ß,ß'-diarylation of the DTP core through C-H activation when reacting unsubstituted H-DTP with 9-anthracenyl halides. For N-substituted DTPs, we obtained regioselective carboxylate-assisted arylation of the α-position(s). Consequently, depending on the catalytic system and substitution at the DTP nitrogen, we successfully synthesized novel regioselectively substituted DTPs, including N-aryl, rarely reported ß-aryl, ß,ß'-diaryl, α-aryl, and α,α'-diaryl scaffolds. These compounds can be straightforwardly prepared and further functionalized for applications as organic electronic materials.

Chiral Phosphoric Acid-Catalyzed Enantioselective Synthesis of Axially Chiral Compounds Involving Indole Derivatives.

Indoles are one of the most ubiquitous subclass of N-heterocycles and are increasingly incorporated to design new axially chiral scaffolds. The rich profile of reactivity and N-H functionality allow chemical derivatization for enhanced medicinal, material and catalytic properties. Although asymmetric C-C coupling of two arenes gives the most direct access of axially chiral biaryl scaffolds, this chemistry has been the remit of metal catalysis and works efficiently on limited substrates. Our group has devoted special interest in devising novel organocatalytic arylation reactions to fabricate biaryl atropisomers. In this realm, indoles and derivatives have been reliably used as the arylation partners in combination with azoarenes, nitrosonapthalenes and quinone derivatives. Their efficient interaction with chiral phosphoric acid catalyst as well as the tunability of electronics and sterics have enabled excellent control of stereo-, chemo- and regioselectivity to furnish diverse scaffolds. In addition, indoles could act as nucleophiles in desymmetrization of 1,2,4-triazole-3,5-diones. This account provides a succinct illustration of these developments.

Isoindigo-Based Dual-Acceptor Conjugated Polymers Incorporated Conjugation Length and Intramolecular Charge Transfer for High-Efficient Photothermal Conversion.

Photothermal tumor therapy (PTT) and photoacoustic imaging (PA) have emerged as promising noninvasive diagnostic and therapeutic approaches for cancer treatment. However, the development of efficient PTT agents with high photostability and strong near-infrared (NIR) absorption remains challenging. This study synthesizes three isoindigo-based dual-acceptor conjugated polymers (CPs) (P-IIG-TPD, P-IIG-DPP, and P-IIG-EDOT-BT) via a green and nontoxic direct arylation polymerization (DArP) method and characterizes their optical, electrochemical, and NIR photothermal conversion properties. By incorporating two acceptors into the backbone, the resulting polymers exhibit enhanced photothermal conversion efficiency (PCE) due to improved synergy among conjugation length, planarity, and intramolecular charge transfer (ICT). The nanoparticles (NPs) of P-IIG-EDOT-BT and P-IIG-DPP have a uniform size distribution around 140 nm and exhibit remarkable NIR absorption at 808 nm. In addition, P-IIG-EDOT-BT and P-IIG-DPP NPs exhibit high PCEs of 62% and 78%, respectively. This study promotes the molecular design of CPs as NIR photothermal conversion materials and provides guidance for the development of novel dual-acceptor CPs for tumor diagnosis and treatment.

Conjugated Polymers from Direct Arylation Polycondensation of 3,4-Difluorothiophene-Substituted Aryls: Synthesis and Properties.

3,4-Difluorothiophene-substituted aryls, i.e., 1,4-bis(3,4-difluorothiophen-2-yl)-benzene (Ph-2FTh), 1,4-bis(3,4-difluorothiophen-2-yl)-2,5-difluorobenzene (2FPh-2FTh), and 4,7-bis(3,4-difluorothiophen-2-yl)-2,1,3-benzothiadiazole (BTz-2FTh), are synthesized as C─H monomers for the synthesis of conjugated polymers (CPs) via direct arylation polycondensation (DArP) with diketopyrrolopyrrole (DPP) and isoindigo (IID) derivatives as C─Br monomers. The Gibbs free energies of activation for direct arylation (ΔG298 K , kcal mol-1 ) for α─C─H bonds of thiophene moieties as calculated by density functional theory (DFT) are 14.3, 16.5, and 16.4 kcal mol-1 for Ph-2FTh, 2FPh-2FTh and BTz-2FTh, respectively, meaning that inserting an electron-deficient unit in 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT, ΔG298K : 14.6 kcal mol-1 ) may cause a reactivity decrease of the C─H monomers. Photophysical and semiconducting properties of the resulting six CPs (i.e., DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz) are characterized in detail. DPP-based CPs show ambipolar transport properties while IID-based ones exhibited n-type behavior owing to the deeper frontier molecular orbital energy levels of IID-based CPs. With source/drain electrodes modified with polyethylenimine ethoxylated, n-channel organic thin-film transistors with maximum electron mobility of 0.40, 0.54, 0.29, 0.05, 0.16, and 0.01 cm2 V-1 s-1 for DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz, respectively, are fabricated. DPP-2FPh exhibits the best device performance due to the good film morphology and the highest intermolecular packing order.

Synthesis and in Vitro Cytotoxicity Evaluation of Jadomycins.

Jadomycins, which are benzo[b]phenanthridine-type alkaloids isolated from Streptomyces venezuelae ISP5230, exhibit cytotoxic activity against multidrug-resistant breast cancer cells. We have previously achieved the total synthesis of jadomycins using the direct arylation of juglone as a key step. In this study, we achieved the total synthesis of jadomycin T and jadomycin aglycons using L-threonine and 1-amino-2-propanol as nitrogen sources. Additionally, we evaluated the cytotoxic activity of eight compounds, including glycosides, jadomycin T, and their corresponding aglycons, in eight types of tumor cells. The evaluated jadomycins tended to exhibit stronger cytotoxic activity as aglycons than as glycosides. Although the presence of a 1,3-oxazolidine ring derived from an amino acid was not essential, the presence of the 1,3-oxazolidine ring showed strong activity when the ring had a carboxyl group. Furthermore, compared to the non-natural isomer at a different position on the phenolic hydroxyl group, the naturally occurring phenanthroviridin aglycon exhibited stronger cytotoxic activity. In addition, this study suggests that jadomycins may become lead compounds for the treatment of brain tumors; however, further studies on their ability to penetrate the blood-brain barrier are required.

Direct Arylation Synthesis of Small Molecular Acceptors for Organic Solar Cells.

In recent years, small molecular acceptors (SMAs) have extensively promoted the progress of organic solar cells (OSCs). The facile tuning of chemical structures affords SMAs excellent tunability of their absorption and energy levels, and it gives SMA-based OSCs slight energy loss, enabling OSCs to achieve high power conversion efficiencies (e.g., >18%). However, SMAs always suffer complicated chemical structures requiring multiple-step synthesis and cumbersome purification, which is unfavorable to the large-scale production of SMAs and OSC devices for industrialization. Direct arylation coupling reaction via aromatic C-H bonds activation allows for the synthesis of SMAs under mild conditions, and it simultaneously reduces synthetic steps, synthetic difficulty, and toxic by-products. This review provides an overview of the progress of SMA synthesis through direct arylation and summarizes the typical reaction conditions to highlight the field's challenges. Significantly, the impacts of direct arylation conditions on reaction activity and reaction yield of the different reactants' structures are discussed and highlighted. This review gives a comprehensive view of preparing SMAs by direct arylation reactions to cause attention to the facile and low-cost synthesis of photovoltaic materials for OSCs.

A High-Performance n-Type Thermoelectric Polymer from C-H/C-H Oxidative Direct Arylation Polycondensation.

n-Type conjugated polymers (CPs) are crucial in the applications of organic electronics. Direct coupling of electron-deficient C-H monomer via selective C-H activation, namely C-H/C-H oxidative direct arylation polycondensation (Oxi-DArP), is an ideal approach toward such CPs. Herein, Oxi-DArP is firstly adopted to synthesize a high-performance n-type CP using a newly developed monomer, i.e., 3,6-di(thiazol-5-yl)-diketopyrrolopyrrole (Tz-5-DPP). Tz-5-DPP based homopolymer PTz-5-DPP with a molecular weight of 22 kDa has been synthesized via Oxi-DArP. After n-doping, PTz-5-DPP films exhibited electric conductivity values up to 8 S cm-1 and power factors (PFs) up to 106 µW m-1 K-2 . Notably, this PF value is the highest for n-type polymer thermoelectric materials to date. The Oxi-DArP synthesis and the excellent n-type performance of the polymer make this work an important step toward the straightforward and sustainable preparation of high-performance n-type polymer semiconductors.

An Efficient Direct Arylation Polycondensation via C-S Bond Cleavage.

The direct arylation polycondensation (DArP) has become one of the most important methods to construct conjugated polymers (CPs). However, the homocoupling side-reactions of aryl halides and the low regioseletive reactivities of unfunctionalized aryls hinder the development of DArP. Here, an efficient Pd and Cu co-catalyzed DArP was developed via inert C-S bond cleavage of aryl thioethers, of which robustness was exemplified by over twenty conjugated polymers (CPs), including copolymers, homopolymers, and random polymers. The capture of oxidative addition intermediate together with experimental and theoretic results suggested the important role of palladium (Pd) and copper (Cu) co-catalysis with a bicyclic mechanism. The studies of NMR, molecular weights, trap densities, two-dimensional grazing-incidence wide-angle X-ray scattering (2D-GIWAXS), and the charge transport mobilities revealed that the homocoupling reactions were significantly suppressed with high regioselectivity of unfunctionalized aryls, suggesting this method is an excellent choice for synthesizing high performance CPs.

Discovery of tricyclic HIV-1 integrase-LEDGF/p75 allosteric inhibitors by intramolecular direct arylation reaction.

We have been conducting exploratory research to develop human immunodeficiency virus type-1 (HIV-1) integrase-LEDGF/p75 allosteric inhibitors (INLAIs). Here, we report on a newly designed compound with a tricyclic scaffold that shows promise as an inhibitor. Various scaffolds were synthesized by intramolecular direct arylation reaction to fix the position of a lipophilic side chain required for antiviral activity. Among these, the compound having an N-mesyl dihydrophenanthridine ring showed the best antiviral activity. Compound 42i, prepared by side chain optimization of the C-4 and C-6 positions, exhibited high antiviral activity against wild-type (WT) and the T174I mutant (EC50 (WT) = 4.6 nM, EC50 (T174I) = 83 nM) with a good PK profile. Based on co-crystal structural analysis of compound 42i and WT HIV-1 IN CCD, we discuss the interaction important for high antiviral activity.

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 ß-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 OSC devices 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.

Ligandless Palladium-Catalyzed Direct C-5 Arylation of Azoles Promoted by Benzoic Acid in Anisole.

The palladium-catalyzed direct arylation of azoles with (hetero)aryl halides is nowadays one of the most versatile and efficient procedures for the selective synthesis of heterobiaryls. Although this procedure is, due to its characteristics, also of great interest in the industrial field, the wide use of a reaction medium such as DMF or DMA, two polar aprotic solvents coded as dangerous according to environmental, health, safety (EHS) parameters, strongly limits its actual use. In contrast, the use of aromatic solvents as the reaction medium for direct arylations, although some of them show good EHS values, is poorly reported, probably due to their low solvent power against reagents and their potential involvement in undesired side reactions. In this paper we report an unprecedented selective C-5 arylation procedure involving anisole as an EHS green reaction solvent. In addition, the beneficial role of benzoic acid as an additive was also highlighted, a role that had never been previously described.

Carbazole and Diketopyrrolopyrrole-Based D-A π-Conjugated Oligomers Accessed via Direct C-H Arylation for Opto-Electronic Property and Performance Study.

Five carbazole and diketopyrrolopyrrole-based donor-acceptor (D-A) new π-conjugated oligomers (π-COs) with gradually elongated lengths are facilely synthesized via a single pot of direct C-H arylation with merits of atom- and step-economy. The structure-property-performance correlations of these π-COs and their parent polymer are studied in detail by opto-electronic characterizations and bulk heterojunction (BHJ) organic photovoltaic (OPV) devices. It is found that the π-COs having longer lengths enable better performance in OPVs owing to the enhanced intermolecular interaction with the elongation of the conjugations. The above results not only highlight the powerful synthetic strategy here provided, but also reveal that π-COs with unique properties might find promising application in OPVs.

Porous Organic Phenanthroline-Based Polymer as an Efficient Transition-Metal-Free Heterogeneous Catalyst for Direct Aromatic C-H Activation.

Direct C-H bond transformation has been regarded as one of the most important areas in organic synthesis in both academia and industry. However, the heterogeneous transition-metal-free catalysis of direct C-H bond transformation has remained a contemporary challenge. To tackle this challenge, we designed and constructed a porous phenanthroline-based polymer (namely POP-Phen) via free radical polymerization of vinyl-functionalized phenanthroline monomers. POP-Phen shows excellent catalytic performances in transition-metal-free catalyzed C-H arylation, even better than those of the corresponding homogeneous catalyst, which is mainly attributed to the high density of catalytically active sites in the heterogeneous catalyst. Kinetic isotope experiments and spectral characterizations demonstrate the electron-transfer between the heterogeneous catalyst and the base (t-BuOK), a key step for C-H activation. We believe that this porous organic phenanthroline polymer could open a new door for the design of novel heterogeneous transition-metal-free catalysts for direct C-H activation.

Step-Economical Synthesis of Conjugated Polymer Materials Composed of Three Components: Donor, Acceptor, and π Units.

Conjugated polymers have immense potential for their use as semiconducting materials in organic optoelectronic devices. The improvement of synthetic methods for conjugated polymers is important for the practical application of conjugated polymers. For mass production, synthetic methods must be developed by considering the concerns regarding cost and environment. Reduction in the number of synthetic steps is an efficient approach to address these concerns. The utilization of direct CH functionalization is a reasonable strategy in monomer and polymer syntheses, because the prefunctionalization steps for CC bond formation can be eliminated. This review summarizes the recent developments in the efficient syntheses of conjugated polymers as well as their monomers via direct arylation (CH/CX coupling) and cross-dehydrogenative coupling (CH/CH coupling) reactions.

Direct Arylation in the Presence of Palladium Pincer Complexes.

Direct arylation is an atom-economical alternative to more established procedures such as Stille, Suzuki or Negishi arylation reactions. In comparison with other palladium sources and ligands, the use of palladium pincer complexes as catalysts or pre-catalysts for direct arylation has resulted in improved efficiency, higher reaction yields, and advantageous reaction conditions. In addition to a revision of the literature concerning intra- and intermolecular direct arylation reactions performed in the presence of palladium pincer complexes, the role of these remarkably active catalysts will also be discussed.