Stille Coupling Research Articles

Front Cover: Recombinant Peptide Fusion Protein‐Templated Palladium Nanoparticles for Suzuki‐Miyaura and Stille Coupling Reactions (ChemCatChem 11/2020)

The Front Cover shows recombinant peptide fusion protein-directed palladium nanoparticles that are catalytically active for Suzuki-Miyaura and Stille coupling reactions in green solvent. In their Communication, I. Mosleh et al. show that metal-binding peptides remain functional after fusing to a green fluorescent protein (GFPuv). This work opens the possibility to use inexpensive peptide sources and shows their ability with palladium to synthesize the anticancer drug Tykerb® precursor. We are grateful to M. A. Ziba Rajabi for designing the cover image. More information can be found in the Communication by I. Mosleh et al.

Bis(thien‐2‐yl)‐2,1,3‐benzothiadiazole‐diketopyrrolopyrrole‐based acceptor–acceptor conjugated polymers: Design, synthesis, and the synergistic effect of the substituent on their solar cell properties

AbstractThree acceptor–acceptor conjugated copolymers (TBT‐DPP, FTBT‐DPP, and HFTBT‐DPP) with different substituent groups have been synthesized with palladium‐catalyzed Stille coupling condensation polymerization assisted with microwave. Polymer solar cells (PSCs) based on these copolymers as the electron donors and PC71BM as the acceptor have been fabricated. The synergistic effect of the substituent between two fluorine atoms and hexyl alkyl chains in bis(thien‐2‐yl)‐2,1,3‐benzothiadiazole fragment on their solar cell properties has been investigated. Both the fluorine atoms and the synergistic effect can improve the solubility of the polymers effectively while the excellent thermal stability properties are still retained. Two fluorine atoms (polymer FTBT‐DPP) increased the power conversion efficiency of the PSCs twice compared with TBT‐DPP (without substituent). The synergistic effect (polymer HFTBT‐DPP) decreased that seriously to zero. Density function theory calculations showed that the conjugation level of the polymer backbone is one of key factors. It demonstrates that the synergistic effect of fluorine atoms and alkyl chains in the same fragment does not always work well in improving the PSCs performance.

Pyrene-benzo[1,2,5]thiadiazole based conjugated polymers for application in BHJ solar cells

Ethylhexyloxy-functionalised pyrene (PEH) was prepared and copolymerised with both dithienyl-benzo[c]-[1,2,5]thiadiazole and dibithiophenyl-benzo[c]-[1,2,5]thiadiazole via a Stille coupling polymerisation method to yield PPEH-DTBT-8 and PPEH-DT2BT-8, respectively. A comparative study was conducted to assess the impact of substituting thiophene for bithiophene repeat units upon the resulting properties of the conjugated polymers. PPEH-DT2BT-8 which has bithiophene spacers between pyrene and benzothiadiazole repeat units, exhibited a narrower optical and electrochemical band gap relative to PPEH-DTBT-8; a consequence of the incorporating bithiophene spacer units which promote intramolecular charge transfer between the electron donating and electron accepting moieties. Both PPEH-DTBT-8 and PPEH-DT2BT-8 showed deep HOMO levels of −5.54 and −5.50 eV, respectively. The polymers possess good thermal stabilities with degradation temperatures in excess of 310 °C. The photovoltaic performance of the two polymers was studied by fabricating bulk heterojunction (BHJ) photovoltaic devices using PC70BM as the acceptor. PPEH-DTBT-8 and PPEH-DT2BT-8 demonstrated efficiencies of 0.33 and 1.83%, respectively. The higher efficiency of PPEH-DT2BT-8 can be attributed to vastly improved FF and Jsc values.

Palladium-Catalysed Coupling Reactions En Route to Molecular Machines: Sterically Hindered Indenyl and Ferrocenyl Anthracenes and Triptycenes, and Biindenyls.

Pd-catalysed Stille and Suzuki cross-couplings were used to prepare 9-(3-indenyl)-, 6, and 9-(2-indenyl)-anthracene, 7; addition of benzyne led to the 9-Indenyl-triptycenes, 8 and 9. In 6, [4 + 2] addition also occurred to the indenyl substituent. Reaction of 6 through 9 with Cr(CO)6 or Re2(CO)10 gave their M(CO)3 derivatives, where the Cr or Re was complexed to a six- or five-membered ring, respectively. In the 9-(2-indenyl)triptycene complexes, slowed rotation of the paddlewheel on the NMR time-scale was apparent in the η5-Re(CO)3 case and, when the η6-Cr(CO)3 was deprotonated, the resulting haptotropic shift of the metal tripod onto the five-membered ring also blocked paddlewheel rotation, thus functioning as an organometallic molecular brake. Suzuki coupling of ferrocenylboronic acid to mono- or dibromoanthracene yielded the ferrocenyl anthracenes en route to the corresponding triptycenes in which stepwise hindered rotations of the ferrocenyl groups behaved like molecular dials. CuCl2-mediated coupling of methyl- and phenyl-indenes yielded their rac and meso 2,2′-biindenyls; surprisingly, however, the apparently sterically crowded rac 2,2′-Bis(9-triptycyl)biindenyl functioned as a freely rotating set of molecular gears. The predicted high rotation barrier in 9-phenylanthracene was experimentally validated via the Pd-catalysed syntheses of di(3-fluorophenyl)anthracene and 9-(1-naphthyl)-10-phenylanthracene.

A novel Strategy of Lock-in Effect between Conjugated Polymer and TiO2 towards Dramatic Enhancement of Photocatalytic Activity under Visible Light

To design novel conjugated polymers and improve interfacial interaction with semiconductor is one of directions to develop high-efficient photocatalysts with harvesting photons and boosting catalytic activities. Herein, two novel linear conjugated polymers poly[(thiophene-ethylene-thiophene)-thiophene] (PTET-T) and poly[(thiophene-ethylene-thiophene)-thiophene-3-carboxylic acid] (PTET-T-COOH) were successfully synthesized by a simple Stille coupling reaction. Their heterojunction with TiO2, i.e, PTET-T/TiO2 (C1) and PTET-T-COOH/TiO2 (C2), exhibited outstanding photocatalytic activity for degrading Rhodamine B, methylene blue and tetracycline. The energetic “lock-in effect” between PTET-T-COOH and TiO2 through carboxyl groups and hydroxyl groups interaction has been proved to greatly improve the interface charge transfer ability and suppress the electron-hole recombination in PTET-T-COOH/TiO2. Thus, by regulating the dosage of polymers, the 15% PTET-T-COOH/TiO2 showed the optimized photocatalytic activity with excellent chemical stability, and its kinetic rate constant was determined to be 41.7 times of that of TiO2. This work provided a new effective strategy of designed and explored organic semiconductor-inorganic heterojunction photocatalysts with broaden absorption, repeatability and high-charge mobility.

Naphthalene imide dimer as interface engineering material: An efficient strategy for achieving high-performance perovskite solar cells

How to design and synthesize interfacial engineered materials that have efficient surface passivation and electron extraction properties is an important problem in the field of optoelectronic materials. Herein, a simple naphthalene imide dimer, namely 2FBT2NDI, is developed by Stille coupling reaction with a high yield, and it is used as interface engineering material for inverted perovskite solar cells (PSCs). Owing to the existence of intermolecular interactions between MAPbI3 and the 2FBT2NDI layer, the introduction of the interfacial layer can passivate the surface defects of perovskite film and improve interface contact. In addition, 2FBT2NDI exhibits suitable energy levels and high electron mobility because of its large linear conjugated skeleton containing two fluorine atoms, which are beneficial for electron extraction for efficient PSCs. By employing 2FBT2NDI as an interfacial layer, inverted PSCs show a maximum power conversion efficiency of 20.1%, which is over 14% higher than that of the control devices without interfacial layer (17.1%). These results highlight that the naphthalene imide dimer can potentially be used as a commercializable interfacial material for achieving high-performance PSCs.

Stitching up the Belt[n]arenes

A synthetic strategy reported recently in the Journal of the American Chemical Society by Wang and coworkers, who used laser irradiation in the final key step of the synthesis, has led to the formation of highly strained belt[8]arene derivatives. This breakthrough could open doors to more controlled and precise syntheses of zigzag carbon nanotubes.

Triethylene Glycol Substituted Diketopyrrolopyrrole‐ and Isoindigo‐Dye Based Donor–Acceptor Copolymers for Organic Light‐Emitting Electrochemical Cells and Transistors

AbstractTriethylene glycol, a common side chain, is attached to two different dye moieties, diketopyrrolopyrrole (DPP) and isoindigo (II), and their bromo derivative monomers are copolymerized, respectively, with common bisstannyl alkylated bithiophene via Stille coupling. The resulting donor–acceptor low‐bandgap copolymers, namely, PTDPP‐DT and PTII‐DT, are rationally deigned and synthesized conjugated polymeric systems suitable for doping. Both polymers are successfully investigated as single‐component and composite‐system‐based electrochemical transistors and light‐emitting electrochemical cells. A PTDPP‐DT thin film exhibits relatively high electrical conductivity of up to 80 S cm−1 in the electrochemically doped state, whereas PTII‐DT thin film prevents the macroscopic charge transport due to a large‐scale crystalline disorientation. Upon evaluating both polymers as active conjugated materials in light‐emitting electrochemical cells, they both exhibit emission under efficient electron/hole doping conditions.

Synthesis and Characterization of Poly(triethylsilylethynylanthradithiophene-bithiazole) for Organic Thin Film Transistor

The new donor-acceptor copolymer with triethylsilylethynylanthradithiophene as donor and bithiazole as acceptor, poly(triethylsilylethynylanthradithiophene-bithiazole) (PTesADT-BTz), was synthesized through stille coupling. The structure of obtained polymer was characterized by H NMR and FT-IR. The number average molecular weight (Mn) and weight average molecular weight (Mw) were measured to be 13 and 23 kDa, respectively, and the polydispersity index was 1.76. The polymer was analyzed by UV-visible spectroscopy, cyclovoltammetry, thermogravimetric analysis, and differencial scanning calorimetry. The organic field effect transistor (OFET) employing PTesADTBTz spin-cast from chloroform solutions at 100 °C annealing showed the mobility of 4.93 × 10−6 cm2/V·s, on/off ratio of 2.20 × 102, and a threshold voltage of 29.7 V.

Design and Synthesis of Benzene Congeners of Resolvin E2, a Proresolving Lipid Mediator, as Its Stable Equivalents.

Resolvins (Rvs) are highly potent anti-inflammatory lipid mediators that are chemically and biologically unstable because of their polyunsaturated structures. To address this issue, we designed benzene congeners of RvE2, i.e., o-, m-, and p-BZ-RvE2s, as stable equivalents of RvE2 by replacing the unstable skipped diene moiety with a benzene ring on the basis of computational conformation studies and synthesized these congeners via a short common route through two Stille couplings. o-BZ-RvE2 exhibited more potent anti-inflammatory activity and much higher metabolic stability than RvE2. Thus, o-BZ-RvE2 was identified as a stable equivalent of RvE2, which is useful as a lead for anti-inflammatory drugs with a new mechanism of action as well as a biotool for investigating RvE2-mediated inflammation resolving pathways.

Ligand-Free and Solvent-Free Synthesis of 1,3-Disubstituted Naphthalenes through Stille Coupling

A variety of 1,3-disubstituted naphthalenes have been prepared by palladium-catalyzed annulation of (o-ethynylphenyl)acetyl chloride with design of a new synthetic strategy by Stille coupling using functionalized organostannanes. The method affords excellent yields of the substituted naphthalenes and accommodates a wide variety of functional groups under mild conditions. Mechanistic studies show intramolecular cyclization as a major step following C–C bond coupling.

Recombinant Peptide Fusion Protein‐Templated Palladium Nanoparticles for Suzuki‐Miyaura and Stille Coupling Reactions

AbstractThis study examined the use of nanoparticles created with recombinant 45‐amino acid long peptides fused to green fluorescent protein (GFPuv) to catalyze twelve representative Suzuki‐Miyaura and Stille coupling reactions. A method was developed to prepare powders (Pd@GFP) containing protein and synthesized nanoparticles. Next, coupling reactions were performed in a green solvent without nanoparticle purification. Pd@GFP had high turnover frequencies for the synthesis of model compounds including lapatinib (Tykerb®) and could be recycled. This study establishes a potentially cost‐effective approach to prepare heterogeneous catalysts containing well‐defined nanoparticles enabling key C−C bond formation leading to synthetically and pharmaceutically interesting compounds.

Effect of cyano substituent on photovoltaic properties of quinoxaline-based polymers

Three donor-acceptor type quinoxaline-based conjugated polymers, in which electron-donating indacenodithiophene (IDT) and indacenodithieno[3,2-b]thiophene (IDTT) were connected to the electron-accepting 2,3-diphenylquinoxaline (DPQ) derivatives, were synthesized using the Stille coupling reaction. To investigate the effects of the strong electron-withdrawing cyano (CN) substituent on the photovoltaic properties of polymers, it was selectively introduced in the DPQ unit on the polymer backbone. The combination of IDT and the standard DPQ produced the reference polymer IDT-Qx, while the coupling of IDT and IDTT with mono-CN substituted DPQ provided the target polymers IDT-QxCN and IDTT-QxCN, respectively. Owing to the significant contributions of the CN substituent, IDT-QxCN and IDTT-QxCN exhibited better photovoltaic performances than IDT-Qx reference. Furthermore, the presence of more planar two thieno[3,2-b] thiophenes in IDTT than the two thiophenes in IDT allowed IDTT-QxCN to display the highest power conversion efficiency (5.47%) with an open circuit voltage of 0.95V, short-circuit current density of 15.30mAcm−2, and fill factor of 56.95%.

Synthesis of (±)-Saudin

Key words (±)-saudin - [2+2] cycloaddition - Stille cross-coupling - Michael addition–aldol addition cascade

Chagosensine: A Riddle Wrapped in a Mystery Inside an Enigma.

The marine macrolide chagosensine is supposedly distinguished by a (Z,Z)-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also incorporates two trans-2,5-disubstituted tetrahydrofuran (THF) rings; this array is unique. After our initial synthesis campaign had shown that the originally proposed structure is incorrect, the published data set was critically revisited to identify potential mis-assignments. The “northern” THF ring and the anti-configured diol in the “southern” sector both seemed to be sites of concern, thus making it plausible that a panel of eight diastereomeric chagosensine-like compounds would allow the puzzle to be solved. To meet the challenge, the preparation of the required building blocks was optimized, and a convergent strategy for their assembly was developed. A key role was played by the cobalt-catalyzed oxidative cyclization of alken-5-ol derivatives (“Mukaiyama cyclization”), which is shown to be exquisitely chemoselective for terminal alkenes, leaving even terminal alkynes (and other sites of unsaturation) untouched. Likewise, a palladium-catalyzed alkyne alkoxycarbonylation reaction with formation of an α-methylene-γ-lactone proved instrumental, which had not found application in natural product synthesis before. Further enabling steps were a nickel-catalyzed “Tamaru-type” homocrotylation, stereodivergent aldehyde homologations, radical hydroindation, and palladium-catalyzed alkyne-1,2-bis-stannation. The different building blocks were assembled in a serial fashion to give the idiosyncratic chlorodienes by an unprecedented site-selective Stille coupling followed by copper-mediated tin/chlorine exchange. The macrolactones were closed under forcing Yamaguchi conditions, and the resulting products were elaborated into the targeted compound library. Yet, only one of the eight diastereomers turned out to be stable in the solvent mixture that had been used to analyze the natural product; all other isomers were prone to ring opening and/or ring expansion. In addition to this stability issue, our self-consistent data set suggests that chagosensine has almost certainly little to do with the structure originally proposed by the isolation team.

A General Approach to Stereospecific Cross-Coupling Reactions of Nitrogen-Containing Stereocenters

A novel strategy employing cyclohexyl spectator ligands in Stille cross-coupling reactions has been developed as a general solution to the long-standing challenge of conducting stereospecific cross-coupling reactions at nitrogen-containing stereocenters. This method enables direct access to enantioenriched products that are difficult (or impossible) to obtain via alternative preparative methods. Selective and predictable transfer of a single secondary alkyl unit can be achieved under reaction conditions that exploit subtle electronic differences between activated and unactivated alkyl units. Through this approach, enantioenriched α-stannylated nitrogen-containing stereocenters undergo Pd-catalyzed arylation and acylation reactions with exceptionally high stereofidelity in all instances investigated. We demonstrate this process by using α-stannylated pyrrolidine, azetidine, and open-chain (benzylic and non-benzylic) nucleophiles in stereospecific reactions. This process will facilitate rapid and reliable access to enantioenriched compounds possessing nitrogen-substituted stereocenters, which constitute ubiquitous structural motifs in biologically active compounds emerging from the drug-discovery process.

Ultra-low-band gap thienoisoindigo-based ambipolar type neutral green copolymers with ProDOT and thiophene units as NIR electrochromic materials

In this paper, thiophene and alkyl substituted propylenedioxythiophene (ProDOT) are taken as the donor units and the alkyl substituted thienoisoindigo (TIIG) unit is adopted as the electron deficient unit. The three donor-acceptor (D-A) type polymers were synthesized via Stille coupling polymerization at the molar feed ratio of 3:2:1, 2:1:1 and 3:1:2 (Thiophene:TIIG:ProDOT), namely as PTIIG-1, PTIIG-2, and PTIIG-3, respectively. The electrochemical band gaps are 0.96, 0.95 and 0.99 eV as the TIIG content decreases. The optical band gaps of the polymers are obtained by the UV–Vis–NIR analysis, and the data are 0.92, 0.94 and 0.98 eV as the TIIG content decreases, suggesting that all polymers belong to the ultra-low-band gap polymers. PTIIG-1 and PTIIG-2 showed neutral green color and oxidized blue color. Polymer PTIIG-3 is an exception, which exhibited a brown color in neutral state and a blue color in oxidized state. At the n-doping state, three polymers exhibited a greyish-white color. As electrochromic polymers, they not only have multicolor properties, but also have excellent kinetic characteristics. Three polymers all exhibited fast response time lower than 1 s in a 4 s time interval, stable optical contrast of 18–25% in 440–870 nm and 58–72% in NIR, large coloration efficiency of 102–254 cm 2 C -1 in 440–870 nm and 404–612 cm 2 C -1 in NIR. The results of electrochemical and optical curves, spectroelectrochemical and electrochromic behaviors showed that the three TIIG-based polymers had potential application in NIR electrochromic areas. • Three low band gap polymers were obtained based on thienoisoindigo, ProDOT and thiophene units. • They all possessed ambipolar property. • Three polymers all exhibited perfect switching performance, especially in the NIR region. • All polymers changed from neutral green to oxidized blue, also showed color changes upon n-doping.

The Introduction of the Radical Cascade Reaction into Polymer Chemistry: A One-Step Strategy for Synchronized Polymerization and Modification.

SummaryPolymerization and modification play central roles in polymer chemistry and are generally implemented in two steps, which suffer from the time-consuming two-step strategy and present considerable challenge for complete modification. By introducing the radical cascade reaction (RCR) into polymer chemistry, a one-step strategy is demonstrated to achieve synchronized polymerization and complete modification in situ. Attributed to the cascade feature of iron-catalyzed three-component alkene carboazidation RCR exhibiting carbon-carbon bond formation and carbon-azide bond formation with extremely high efficiency and selectivity in one step, radical cascade polymerization therefore enables the in situ synchronized polymerization through continuous carbon-carbon bond formation and complete modification through carbon-azide bond formation simultaneously. This results in a series of α, β, and γ poly(amino acid) precursors. This result not only expands the methodology library of polymerization, but also the possibility for polymer science to achieve functional polymers with tailored chemical functionality from in situ polymerization.

Simultaneously enhancing the dielectric constant, photo-response and deepening HOMO levels of benzo[1,2-b;4,5-b']dithiophene derivatives-based conjugated polymers

An alternating conjugated polymer (CPs) named as PBDT-TS-DPP, derived from 2-ethylhexylthiothiophen-2-yl-flanked (TS) benzo[1,2-b;4,5-b']dithiophene (BDT-TS) and diketopyrrolopyrrole derivatives (DPP), was prepared by Palladium-catalyzed Stille coupling reaction. The comparison investigations of the opto-electronic properties and aggregation characteristics between the PBDT-TS-DPP and PBDT-T-DPP, which was derived from 2-ethylhexylthiophen-2-yl-flanked (T) benzo[1,2-b;4,5-b']dithiophene (BDT-T) and DPP, were implemented. The results indicated that the PBDT-TS-DPP not only presented narrower optical band gap, deeper HOMO energy levels, similar charger transporting and aggregation characteristics etc., but also held enhanced relative dielectric constant (εr) in relative to that for the PBDT-T-DPP. To our knowledge, it is firstly to verify that the replacement of T with TS flanks would result in the enhancing εr besides the deepening HOMO energy levels and broadening the light response range for the BDT based CPs. Beyond that, the inverted photovoltaic cells (i-OPVs) with power conversion efficiencies (PCEs) of 5.48% and 4.78%, open circuit voltage (VOC) of 0.78 V and 0.74 V, short current density (JSC) of 11.52 mA/cm2 and 9.46 mA/cm2, fill factors (FF) of 61.0% and 68.3%, were respectively presented in PBDT-TS-DPP and PBDT-T-DPP based i-OPVs. Meanwhile, it has also been certified that the i-OPVs from PBDT-TS-DPP exhibited higher exciton dissociation probability, charge carrier density, charger carriers lifetime, and lower recombination rate co-efficiency etc., which might be attributed to the higher dielectric constant of PBDT-TS-DPP as compared with PBDT-T-DPP, thus devote to the additional improvement of the PCEs, VOC and JSC for the PBDT-TS-DPP based i-OPVs, except that the improvement of the these parameters were compensated from the deepening HOMO energy level and broadening light response of the PBDT-TS-DPP.

Intermolecular Diels-Alder Cycloaddition/Cross-Coupling Sequences of 2-Bromo-1,3-butadienes.

2-Bromo-1,3-butadienes are demonstrated to be effective substrates for tandem Diels-Alder/transition metal cross-coupling reaction sequences. Intermolecular cycloaddition of a 2-bromo-1,3-diene with activated dienophiles proceeded under Lewis acid catalysis in generally high yields with good to excellent endo diastereoselectivity. The resulting vinyl bromide cycloadducts underwent subsequent Stille and Suzuki cross-couplings under standard conditions in good yields. Both the Diels-Alder and cross-coupling steps were highly tolerant of a range of functionalities and protecting groups. The use of the bromine substituent as both a cycloaddition directing group and cross-coupling nucleofuge avoids extra steps required to install and remove the more commonly used silyl enol ethers and enol sulfonates for each transformation and gives full control of the alkene regiochemistry throughout the reaction sequence. The 2-bromo-1,3-dienes were conveniently prepared in three steps from readily available aldehydes and established as hydrolytically stable and practical synthetic intermediates.