Mediated Coupling Reaction Research Articles

ChemInform Abstract: Silver(I)‐Mediated Coupling Reaction of Heterocyclic Ketene Aminals (HKAs) with Bis(phenylsulfonyl)sulfides to Synthesis of Benzenesulfonothioyl‐HKAs.

AbstractThe products are prepared in view of new anticancer drugs.

Silver(I)-mediated coupling reaction of heterocyclic ketene aminals (HKAs) with bis(phenylsulfonyl)sulfides to synthesis of benzenesulfonothioyl-HKAs

An efficient and convenient method was developed for the preparation of 2-benzenesulfonothiol-HKAs via a silver(I)-mediated direct sulfenylation of heterocyclic ketene aminals (HKAs). The method involves a variety of functionalized substrates, leading to α-arylthioyl HKAs in a mild, easy operation, and mild reaction conditions.

Tailor-made rylene arrays for high performance n-channel semiconductors.

Rylene dyes, made up of naphthalene units linked in peri-positions, are emerging as promising key building blocks to create π-functional materials. Chemists have found uses for these ribbonlike structures in a wide range of applications of optoelectronic devices. Because their structure combines two sets of six-membered electron-withdrawing dicarboxylic imide rings, rylene diimides exhibit enhanced solubility, excellent chemical and thermal stabilities, high electron affinities, and remarkable electron-transporting properties. Among them, perylene diimide (PDI) and naphthalene diimide (NDI) derivatives are important representatives improving the performance of electron-transporting technologies, relative to their p-channel counterparts. Pioneering works by Müllen and Langhals have inspired chemists to extend the π-conjugation along the peri-positions of rylene diimides, which generally results in impressive bathochromic shifts and a nearly linear increase in the extinction coefficient. In addition, in the past years, researchers have focused on π-expansion of NDI or PDI systems through bay-functionalization with carbocyclic and heterocyclic rings annulated onto the skeleton. However, chemists have rarely investigated lateral expansion via both bay- and nonbay-functionalization to construct homologous series of rylene arrays with different electronic delocalization and fine-tuned flexible linkage. This is probably due to the lack of effective procedures for the (multi) carbon-carbon formation and annulation of electron-deficient rylene imide units. In this Account, we discuss our recent progress in the design and synthesis of laterally expanded rylene dyes based on homocoupling and cross-coupling reactions of core-functionalized PDIs and NDIs to achieve novel high performance n-channel organic semiconducting materials. These new achievements offer us opportunities to learn fundamental issues about how chemical and physical properties alter with incremental changes in structure. We highlight synthetic methodology of transition-metal mediated coupling reactions (and/or C-H transformation) for singly linked, doubly linked, and fully conjugated triply linked oligoPDIs, and further for the construction of hybrid rylene arrays via bay- and/or nonbay-functionalization. In addition, we summarize the informative correlations between the molecular structures and their optoelectronic properties, especially the modulation of progressively red-shifted absorption maxima and positive shifts in the redox potentials. This decreases the energy gaps and increases the electron-accepting abilities through expansion of π-system, which has direct impacts on the compounds' potential applications in optoelectronic devices. Finally, we introduce the promising applications of these laterally expanded rylene dyes as exceptional high performance n-channel semiconductors in organic field-effect transistors (OFETs) and competitive candidates for non-fullerene acceptors in high efficient organic photovoltaic devices (OPVs).

Potassium Tellurocyanate Mediated Coupling Reactions of N-(1-Chloroethylidene)Arylamines

The reaction of potassium tellurocyanate (prepared in situ) with N-(1-chloroethylidene)arylamines (i.e., 4-RC6H4N = C(CH3)Cl, where R = H, Cl, CH3 and NO2) in DMSO solution gave unexpectedly, after hydrolysis, the corresponding N-(3-(arylamino)butan-2-ylidene)arylamines in 63–78%. Reaction of N-(3-(arylamino)butan-2-ylidene)arylamines with SOCl2 or with Br2 resulted in the substitution of a halogen on the aromatic rings. The presence of a water molecule within the structure of the synthesized diimines was rationalized theoretically by Density Functional Theory (DFT). All compounds were characterized by elemental analysis, IR, NMR and mass spectroscopic data.

ChemInform Abstract: A Bromine‐Radical Mediated Three‐Component Reaction Comprising Allenes, Electron‐Deficient Alkenes and Allyl Bromides: Facile Synthesis of 2‐Bromo‐1,7‐dienes.

A bromine-radical mediated three-component coupling reaction was effectively achieved by the use of allenes, electron-deficient alkenes, and allyl bromides and led to the synthesis of 2-bromo-1,7-dienes in good to high yields. This protocol was extended to the three-component process using alkylidenecyclopropane, which gave 2-bromo-1,8-diene along with alkylidenecyclopentane.

Synthesis of ferrocene-based polythiophenes and their applications

Individually, ferrocene and thiophenes have incredible properties and important applications. During the last two decades, scientists synthesized polythiophenes containing ferrocene in the main and side chains. Polythiophenes have redox, conducting, and optical properties. Because of these properties, polythiophenes have been used in sensing applications. In addition, ferrocene has reversible redox properties and accordingly has been used in a lot of sensing devices, such as glucose sensing. Ferrocene can have +2 or +3 oxidation state, which can correspond to “0” and “1”, and thus can be used as a memory storage material. When these two moieties are combined together, they show good compatibility. Therefore, the resulting materials/polymers have been used in memory storage and chemical sensing devices. Thus, we carefully selected studies that are only associated with ferrocene-based polythiophenes. In this review, we tried to focus on the synthesis and applications of ferrocene-based polythiophenes. There are many methods for the polymerization of thiophenes. Here, we discussed the electrochemical polymerization, oxidation polymerization, nickel mediated coupling reactions, and Suzuki polycondensation. In addition, polythiophenes can be decorated with ferrocene, pre- or post-polymerization. These materials were examined for important applications, including information storage, DNA sensing, protein sensing, and glucose sensing materials.

ChemInform Abstract: Synthesis of Novel 9‐Aryl and Heteroarylpurine Derivatives via Copper Mediated Coupling Reaction.

A series of 9-(hetero)arylpurine derivatives has been prepared through N-arylation of 6-chloropurine with boronic acids in the presence of copper(II) acetate. Screening reaction conditions in terms of bases and solvents led to the successful coupling of a series of sterically demanding (hetero)arylboronic acids, never described so far. The coupling products were next readily converted into the target adenine derivatives. The described procedure provides easy access to original fragments for screening applications. Moreover these 9-aryl-6-chloropurine derivatives might be useful as intermediates for the preparation of purine derivatives with potential biological properties.

ChemInform Abstract: Tin(II) Chloride Mediated Coupling Reactions Between Alkynes and Aldehydes.

AbstractTin dichloride mediates the coupling reaction between alkynes and aldehydes as a Lewis acid in nitromethane to stereoselectively produce (E)‐α,β‐unsaturated ketones by a skeletal transformation in which one alkynic carbon atom changes into an oxo carbon atom accompanied by the cleavage of a C=O bond in the starting aldehydes.

ChemInform Abstract: Templated Carbene Metathesis Reactions from the Modular Assembly of Enol‐diazo Compounds and Propargyl Acetates.

A Lewis acid mediated coupling reaction of enol-diazo nucleophiles and propargyl acetates has provided rapid and diverse access to complex alkynyl-tethered diazocarbonyl compounds. The ability of the coupling reaction to vary critical functionality flanking the diazo group was explored as a way to direct the outcome of a series of metal-catalyzed carbene metathesis cascade reactions. These cascade reactions provided diverse, biologically interesting carbocyclic and heterocyclic compounds in only a few steps from readily available materials.

Synthesis of novel 9-aryl and heteroarylpurine derivatives via copper mediated coupling reaction

A series of 9-(hetero)arylpurine derivatives has been prepared through N-arylation of 6-chloropurine with boronic acids in the presence of copper(II) acetate. Screening reaction conditions in terms of bases and solvents led to the successful coupling of a series of sterically demanding (hetero)arylboronic acids, never described so far. The coupling products were next readily converted into the target adenine derivatives. The described procedure provides easy access to original fragments for screening applications. Moreover these 9-aryl-6-chloropurine derivatives might be useful as intermediates for the preparation of purine derivatives with potential biological properties.

A bromine-radical mediated three-component reaction comprising allenes, electron-deficient alkenes and allyl bromides: facile synthesis of 2-bromo-1,7-dienes

A bromine-radical mediated three-component coupling reaction was effectively achieved by the use of allenes, electron-deficient alkenes, and allyl bromides and led to the synthesis of 2-bromo-1,7-dienes in good to high yields. This protocol was extended to the three-component process using alkylidenecyclopropane, which gave 2-bromo-1,8-diene along with alkylidenecyclopentane.

Trypsin-inspired poly(urea-urethane)s containing phenylalanine-lysine ethyl ester-phenylalanine units

Abstract A novel tri-peptide derivative phenylalanine-lysine ethyl ester-phenylalanine (PLP) was synthesized by carbodiimide hydrochloride (EDC·HCl) mediated coupling reaction from phenylalanine and lysine ethyl ester in the presence of NHS. Then PLP was used as a chain extender to synthesize a kind of trypsin-inspired poly(urea-urethane)s (PLP-PU) with polyethylene glycol (PEG) as soft segment and hexamethylene diisocyanate (HDI) as hard segment. Enzymatic degradation tests showed that PLP unit was very sensitive to trypsin in its solution. Experimental results indicated that the degradability was obviously improved by introducing PLP into the main chain of poly(urea-urethane) because the PLP was effectively broken by the action of trypsin in the process of degradation.

ChemInform Abstract: Be Squared: Expanding the Horizon of Squaric Acid‐Mediated Conjugations

AbstractReview: overview of the well‐established squaric acid diester mediated coupling reactions for glycoconjugates and recent advances to expand this very versatile reaction protocol to the modification of peptides and proteins; 101 refs.

Epimerization‐Free C‐Terminal Peptide Activation

Smooth operation: C-terminal peptide activation with full stereointegrity was accomplished using a copper(II)-mediated coupling reaction of carboxylic acids with arylboroxines (see scheme, NCL = native chemical ligation, Boc = tert-butoxycarbonyl). This method allows epimerization-free activation and ligation of peptides with racemization-prone phenylglycine at the C terminus.

Enhanced Brain Delivery of Deferasirox–Lactoferrin Conjugates for Iron Chelation Therapy in Neurodegenerative Disorders: In Vitro and in Vivo Studies

Oxidative stress associated cell damage is one of the key factors in neurodegeneration development and is highly related to the presence of transition metal ions including iron. Herein, deferasirox, a high affinity iron chelator, was conjugated to lactoferrin molecules by carbodiimide mediated coupling reaction to create a novel drug delivery system with higher brain permeability through receptor mediated transcytosis. Each lactoferrin molecule was averagely attached to 4 to 6 deferasirox molecules resulting in water-soluble conjugated nanostructures which were purified and characterized. Neuroprotective effects of lactoferrin conjugated nanostructures and their cellular uptake were evaluated in differentiated PC12 cell line, and the molecular mechanisms involved in such neuroprotection were elucidated. Lactoferrin conjugates were able to interfere in apoptotic caspase cascade by affecting the expression level of caspase-3, PARP, Bax and Bcl-2. Furthermore, an elevation in the expression level of autophagy markers including Atg7, Atg12-Atg5 and LC3-II/LC3-I ratio was observed. Intraperitoneal injection of lactoferrin conjugates was able to significantly attenuate learning deficits induced by beta amyloid injection in a rat model of Alzheimer's disease, which further confirms a potential neuroprotective effect for lactoferrin conjugated deferasirox in neurodegenerative disorder management through metal chelation therapy.

Tin(II) Chloride Mediated Coupling Reactions between Alkynes and Aldehydes

AbstractTin(II) chloride, which is insensitive to water and air, mediated the coupling reaction between alkynes and aldehydes as a Lewis acid in nitromethane to produce (E)‐α,β‐unsaturated ketones by a skeletal transformation in which one alkynic carbon atom changed into an oxo carbon atom accompanied by the cleavage of a C=O bond in the starting aldehydes. This coupling reaction was promoted by a catalytic amount of a primary or secondary alkanol. The coupling reaction between 1‐deuterio‐2‐phenylethyne and benzaldehyde with BuOH afforded 1,3‐diphenyl‐2‐deuterio‐2‐propenone (2‐deuteriation: 94 % D), whereas the coupling reaction between phenylethyne and benzaldehyde with BuOD afforded 1,3‐diphenyl‐2‐propenone (2‐deuteriation: 0 % D). Because almost no exchange between hydrogen and deuterium at the 2‐position of 1,3‐diphenyl‐2‐propenone occurs in either of the reactions, the coupling reaction between alkynes and aldehydes with tin(II) chloride is presumed to proceed by nucleophilic addition of alkynes to aldehydes. The cleavage of the C–O single bond generated by the nucleophilic addition might be induced by the strong oxophilicity of tin.

Templated Carbene Metathesis Reactions from the Modular Assembly of Enol‐diazo Compounds and Propargyl Acetates

AbstractA Lewis acid mediated coupling reaction of enol‐diazo nucleophiles and propargyl acetates has provided rapid and diverse access to complex alkynyl‐tethered diazocarbonyl compounds. The ability of the coupling reaction to vary critical functionality flanking the diazo group was explored as a way to direct the outcome of a series of metal‐catalyzed carbene metathesis cascade reactions. These cascade reactions provided diverse, biologically interesting carbocyclic and heterocyclic compounds in only a few steps from readily available materials.

Amino Acid Grafted Chitosan for High Performance Gene Delivery: Comparison of Amino Acid Hydrophobicity on Vector and Polyplex Characteristics

To develop a safe, effective, and biocompatible gene delivery vector, a series of hydrophobic amino acid grafted chitosan (AGC) derivatives were synthesized by carbodiimide mediated coupling reaction. Chemical characterization of AGC polymers was performed by NMR and elemental analysis. AGC polymers demonstrated excellent blood compatibility and cell viability, as evaluated by hemolysis and MTT assay, respectively. AGC polymers could effectively bind and condense plasmid DNA (pDNA) to form polyplexes in the size range of 161-263 nm and possessed net cationic charge. The resultant polyplex showed 3.4-5.4-fold greater cellular uptake and 13-30-fold higher transfection efficiency in HEK 293 cells as compared to unmodified chitosan. Moreover, both cellular uptake and transfection efficiency improved with the increasing amino acid hydrophobicity. Hydrophobic amino acid substitution contributed to the enhance pDNA release at cytosolic pH. These data demonstrate AGC polymers as a promising novel nonviral gene delivery vector.

Be squared: expanding the horizon of squaric acid-mediated conjugations

Squaric acid diesters can be applied as reagents to couple two amino-functional compounds. Consecutive coupling of two amines allows the synthesis of asymmetric squaric acid bisamides with either low molecular weight compounds but also biomolecules or polymers. The key feature of the squaric acid diester mediated coupling is the reduced reactivity of the resulting ester-amide after the first amidation step of the diester. This allows the sequential amidation and generation of asymmetric squaramides with high selectivity and in high yields. This article gives an overview of the well-established squaric acid diester mediated coupling reactions for glycoconjugates and presents recent advances that aim to expand this very versatile reaction protocol to the modification of peptides and proteins.

New Insights into the Mechanism and an Expanded Scope of the Fe(III)-Mediated Vinblastine Coupling Reaction

A definition of the scope of aromatic substrates that participate with catharanthine in an Fe(III)-mediated coupling reaction, an examination of the key structural features of catharanthine required for participation in the reaction, and the development of a generalized indole functionalization reaction that bears little structural relationship to catharanthine itself are detailed. In addition to providing insights into the mechanism of the Fe(III)-mediated coupling reaction of catharanthine with vindoline suggesting the reaction conducted in acidic aqueous buffer may be radical mediated, the studies provide new opportunities for the preparation of previously inaccessible vinblastine analogs and define powerful new methodology for the synthesis of indole-containing natural and unnatural products.