Palladium(II)‐N‐Heterocyclic Carbene Complexes: Efficient Catalysts for the Direct C‐H Bond Arylation of Furans with Aryl Halides

This paper contains the synthesis and characterization of the seven new benzimidazolium salts and their corresponding new palladium(II)‐NHC complexes with the general formula [PdX₂(NHC)₂], (NHC = N‐heterocyclic carbene, X = Cl or Br), and also their catalytic activity in direct C‐H bond arylation of 2‐substituted furan derivatives with aryl bromides and aryl chlorides. Under the optimal conditions, these palladium(II)‐NHC complexes showed the good catalytic performance for the direct C‐H bond arylation of 2‐substituted furans with (hetero)aryl bromides, and with readily available and inexpensive aryl chlorides. The C‐H bond arylation regioselectively produced C5‐arylated furans by using 1 mol% of the palladium(II)‐NHC catalysts in moderate to high yields.     

Dose‐, time‐and lipophilicity‐dependent silver(I)–N‐heterocyclic carbene complexes: Synthesis,characterization and interaction with plasmid and Aedes albopictus DNA

Four new Ag(I)–N‐heterocyclic carbene (NHC) complexes ( 5 – 8 ) bearing symmetrically substituted NHC ligands have been synthesized starting from the corresponding benzimidazolium bromide salts which are accessible in a single step from N ‐substituted benzimidazoles (N ‐alkyl and N ‐aryl) and subsequently reacted with the basic metal source Ag₂O in acetonitrile–methanol. These compounds were characterized using elemental analyses, ¹H NMR, ¹³C NMR, Fourier transform infrared and UV–visible spectroscopic techniques, and molar conductivity. Single‐crystal structural studies for complex 5 show that the Ag(I) centre has a perfectly linear C–Ag–C coordination, with quasi‐parallel pairs of aromatic benzimidazole planes. All the complexes interact with Aedes albopictus DNA via intercalation mode by a large hypochromicity of 22 and 27% and smaller hypochromicity of 16 and 19%. Furthermore, all complexes exhibit efficient DNA cleavage activity via a non‐oxidative mechanistic pathway. The DNase activities of the test compounds revealed a time‐ and concentration‐dependent activity pattern. The Ag(I)–NHC complexes showed considerably higher DNA cleavage activity compared to their respective benzimidazolium salts at a lower concentration. The DNA cleavage of these complexes changed from a moderate effect to a good one, corresponding to the increasing lipophilicity order of the complexes as 5  <  6  <  7  <  8 (1.02, 1.05, 1.78 and 2.06 for 5 – 8 , respectively). This order is further corroborated with the DNA binding study, but with the exception of complex 5 , which shows a better binding ability for DNA (K _b = 3.367 × 10⁶) than complexes 6 – 8 (6.982 × 10⁵, 8.376 × 10⁵ and 1.223 × 10⁶, respectively).     

N‐heterocyclic carbene–palladium complexes for Suzuki–Miyaura coupling reaction with benzyl chloride and aromatic boronic acid leading to diarylmethanes

A family of N‐heterocyclic carbene–palladium(II)–N,N‐dimethylbenzylamine complexes ((NHC)LPdCl₂; L = N,N‐dimethylbenzylamine) were synthesized as well as characterized using single‐crystal X‐ray diffraction and spectroscopic data. These complexes exhibited higher catalytic activities for the Suzuki reaction of benzyl chlorides to afford diarylmethanes under milder conditions than other efficient (NHC)LPdCl₂ complexes. Using the optimum conditions, the expected coupling products were obtained in moderate to high yields. All reactions were carried out in air and all starting materials were used as supplied without purification.     

Synthesis and Structures of Arene Ruthenium (II)–NHC Complexes: Efficient Catalytic α‐alkylation of ketones via Hydrogen Auto Transfer Reaction

A panel of six new arene Ru (II)‐NHC complexes 2a‐f , (NHC = 1,3‐diethyl‐(5,6‐dimethyl)benzimidazolin‐2‐ylidene 1a , 1,3‐dicyclohexylmethyl‐(5,6‐dimethyl)benzimidazolin‐2‐ylidene 1b and 1,3‐dibenzyl‐(5,6‐dimethyl)benzimidazolin‐2‐ylidene 1c ) were synthesized from the transmetallation reaction of Ag‐NHC with [(η⁶‐arene)RuCl₂]₂ and characterized. The ruthenium (II)‐NHC complexes 2a‐f were developed as effective catalysts for α‐alkylation of ketones and synthesis of bioactive quinoline using primary/amino alcohols as coupling partners respectively. The reactions were performed with 0.5 mol% catalyst load in 8 h under aerobic condition and the maximum yield was up to 96%. Besides, the different alkyl wingtips on NHC and arene moieties were studied to differentiate the catalytic robustness of the complexes in the transformations.     

Synthesis,structural characterization and catalytic activity of benzimidazole‐functionalized Pd(II) N‐heterocyclic carbene complexes

Two Pd(II)–NHC complexes bearing benzimidazole and pyridine groups have been successfully prepared and fully characterized by NMR and X‐ray diffraction analysis. The structure of palladium complexes are a typical square‐planar with palladium surrounded by two pairs of trans‐arranged benzimidazole and carbene ligands. The Pd–NHC complexes have been proved to be a highly efficient catalyst for the Mizoroki–Heck coupling reaction of aryl halides with various substituted acrylates under mild conditions in excellent yields. Copyright © 2013 John Wiley & Sons, Ltd.     

Well‐Defined Amphiphilic C60‐PEG Conjugates: Water‐Soluble and Thermoresponsive Materials

For the preparation of well‐defined H₂O‐soluble C₆₀ polymers, several C₆₀‐PEG conjugates were prepared from a C₆₀ biscarboxylic acid derivative and monodisperse NH₂‐PEGs (NH₂‐EG_n, n = 4 – 36) via amide conjugation. When the relatively long PEGs (EG_n, n ≥ 12) were employed, the C₆₀‐PEG conjugates became completely H₂O‐soluble by forming micelle‐like structure shown by the data of surface tension, DLS, and cryo‐TEM. Interestingly, these H₂O‐soluble C₆₀‐PEG conjugates (C₆₀(EG_n)₂, n = 12 – 36) showed reversible thermoresponse to form larger aggregates (ca. 1 μm by DLS) at higher temperatures. The temperature for the aggregation was related to the lengths of PEGs attached to C₆₀; 29 °C (C₆₀(EG_n)₂, n = 12), 51 °C (n = 20), and 72 °C (n = 36). This thermoresponse was speculated to occur by dehydration of well‐organized PEG chains in the micelle‐type structure of monodisperse C₆₀‐PEG caused by gauche‐to‐anti conformational change of PEG anchors. This thermoresponse of well‐defined amphiphilic C₆₀‐PEG conjugates indicates potential applications in areas such as temperature sensors and thermoresponsive materials.     

Synthesis,reactivity and preliminary biological activity of iron(0) complexes with cyclopentadienone and amino‐appended N‐heterocyclic carbene ligands

Neutral and cationic cyclopentadienone (CpO) N‐heterocyclic carbene (NHC) bis‐carbonyl iron(0) complexes bearing, appended to the NHC ligand, either a terminal amino group on the lateral chain, [Fe(η⁴‐CpO)(CO)₂(κC‐NHC(CH₂)_nNH₂)] with n = 2 ( 2a ) and 3 ( 2b ), or a cationic NMe₃⁺ fragment, [Fe(η⁴‐CpO)(CO)₂(κC‐NHC(CH₂)₂NMe₃)](I) ( 3 ), were prepared and characterized in terms of their structure, stability and reactivity. The photochemical properties of 2a and 2b were examined both in organic solvents and in water, revealing the photoactivated release of one CO ligand followed by the formation of the chelated complex [Fe(η⁴‐CpO)(CO)(κ²C,N‐NHC(CH₂)₂NH₂)] ( 4 ), whose molecular structure was confirmed by single crystal X‐ray diffraction studies. This metallacyclization occurs only in the case of 2a , with the ethylene spacer between NHC ring and NH₂ group in the lateral chain, allowing the formation of a stable 6‐membered ring. On the other hand, 2b undergoes decomposition upon irradiation. The reactivity in aqueous solutions revealed the chemical speciation of the complexes at different pH and especially under physiological conditions (phosphate buffer solution at pH 7.4 and 37 °C). The lack of data on the biological properties of iron(0) complexes prompted us to preliminarily investigate their cytotoxicity against model cancer cells (AsPC‐1 and HPAF‐II), along with a determination of their lipophilicity.     

Trifluoromethylpyridine‐Substituted N‐Heterocyclic Carbenes Related to Natural Products: Synthesis,Structure, and Potential Antitumor Activity of some Corresponding Gold(I), Rhodium(I), and Iridium(I) Complexes

This work presents the synthesis, characterization, and application of several new metal(I) complexes with trifluoromethylpyridine‐containing N‐heterocyclic carbene (NHC) ligands. The metal of choice was gold(I) for compounds 7  –  10 , rhodium(I) for 11  –  12 , and iridium(I) for 13  –  14 , respectively. The trifluoromethylpyridine moiety was incorporated, along with other biologically active moieties, with the intention of modifying the lipophilicity of the complexes, so that the transport of the active units (M–NHC) through the cell wall barrier is facilitated. The biological activity of the complexes was investigated. In vitro assessment of antitumor activity in a panel of 12 human tumor cell lines by a monolayer assay revealed good potency (mean IC₅₀ 12.6 μm ) and tumor selectivity for one compound. The solid‐state structures of two solvates of compound 7 , one with MeOH and one with THF, were determined by X‐ray diffraction analysis.     

Palladium(II)‐N‐heterocyclic carbene complexes: synthesis,characterization and catalytic application

N‐Heterocyclic carbenes (NHCs) are of great importance and are powerful ligands for transition metals. A new series of sterically hindered benzimidazole‐based NHC ligands (LHX) ( 2a , 2b , 2c , 2d , 2e , 2f ), silver–NHC complexes ( 3a , 3b , 3c , 3d , 3e , 3f ) and palladium–NHC complexes ( 4a , 4b , 4c , 4d , 4e , 4f ) have been synthesized and characterized using appropriate spectroscopic techniques. Studies have focused on the development of a more efficient catalytic system for the Suzuki coupling reaction of aryl chlorides. Catalytic performance of Pd–NHC complexes and in situ prepared Pd(OAc)₂/LHX catalysts has been investigated for the Suzuki cross‐coupling reaction under mild reaction conditions in aqueous N,N‐dimethylformamide (DMF). These complexes smoothly catalyzed the Suzuki–Miyaura reactions of electron‐rich and electron‐poor aryl chlorides. Copyright © 2014 John Wiley & Sons, Ltd.     

Enantiopure Cycloiridiated Complexes Bearing a Pentahelicenic N‐Heterocyclic Carbene and Displaying Long‐Lived Circularly Polarized Phosphorescence

A fused π‐helical N‐heterocyclic carbene (NHC) system was prepared and examined through its diastereoisomerically pure cycloiridiated complexes. The latter display light‐green phosphorescence with unusually long lifetimes and circular polarization that depends on both the helical NHC P /M stereochemistry and the iridium Δ/Λ stereochemistry. These unprecedented features are attributed to extended π conjugation within the helical carbenic ligand and efficient helicene‐NHC–Ir interaction.     

Synthesis,characterization and catalytic activity in Suzuki–Miyaura coupling of palladacycle complexes with n‐butyl‐substituted N‐heterocyclic carbene ligands

A series of monomeric palladacycle complexes bearing n‐butyl‐substituted N‐heterocyclic carbenes, namely [Pd(NHC)X(dmba)] (dmba: dimethylbenzylamine and [Pd(NHC)X(ppy)]; NHC: 1‐n‐butyl‐3‐substituted benzylimidazol‐2‐ylidene; ppy: 2‐phenylpyridine), were prepared either by transmetallation from the corresponding silver carbene complexes or by the reaction of the corresponding acetate‐bridged palladacycle dimer with N‐heterocyclic carbene ligands in high yields. The palladium(II) complexes were characterized using elemental analyses, APCI‐MS, ¹H NMR and ¹³C NMR spectroscopies. These complexes are efficient in the Suzuki–Miyaura coupling reaction between phenylboronic acid and aryl bromides.     

Synthesis of 3,3‐Disubstituted Oxindoles by Palladium‐Catalyzed Asymmetric Intramolecular α‐Arylation of Amides: Reaction Development and Mechanistic Studies

Palladium complexes incorporating chiral N‐heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α‐arylation of amides producing 3,3‐disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate‐determining and reductive elimination to be enantioselectivity‐determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8 , containing a tBu and a 1‐naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro‐oxindoles and three azaspiro‐oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X‐ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency.     

Palladium complexes of bidentate pyridine N‐heterocyclic carbenes: Optical resolution,antimicrobial and cytotoxicity studies

A series of bidentate pyridine‐functionalized palladium N‐heterocyclic carbene (Pd NHC) complexes with various wingtip substituents (R = methyl, phenyl and tert‐butyl) have been synthesized and evaluated for their potential biomedical applications as antimicrobials and antiproliferative drug candidates. The obtained Pd NHC complexes were applied in a standard broth microdilution assay for determination of their antimicrobial activities against thirteen strains of pathogenic microorganisms. In addition to that, cytotoxic activities of the Pd NHC complexes were also evaluated against three human cancer cell lines, namely breast (MCF‐7), colon (HCT116) and oral (H103) cancer cells, using a standard MTT assay. Upon coordination to palladium, the Pd NHC complexes show significant antimicrobial activities with minimum inhibitory concentrations in the micromolar range, and they are cytotoxic to the tested carcinomas with IC₅₀ ranging from 13 to 38 μM. Evidences for influence of both wingtip substituents and optical isomerism on the biological activities of the complexes have been found.     

Synthesis,cytotoxicity and antibacterial studies of symmetrically and non‐symmetrically benzyl‐ or p‐cyanobenzyl‐substituted N‐Heterocyclic carbene–silver complexes

From the reaction of 1H‐imidazole ( 1a ), 4,5‐dichloro‐1H‐imidazole ( 1b ) and 1H‐benzimidazole ( 1c ) with p‐cyanobenzyl bromide ( 2 ), symmetrically substituted N‐heterocyclic carbene (NHC) [( 3a–c )] precursors, 1‐methylimidazole ( 5a ), 4,5‐dichloro‐1‐methylimidazole ( 5b ) and 1‐methylbenzimidazole ( 5c ) with benzyl bromide ( 6 ), non‐symmetrically substituted N‐heterocyclic carbene (NHC) [( 7a–c )] precursors were synthesized. These NHC? precursors were then reacted with silver(I) acetate to yield the NHC‐silver complexes [1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4a ), [4,5‐dichloro‐1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4b ), [1,3‐bis(4‐cyanobenzyl)benzimidazole‐2‐ylidene] silver(I) acetate ( 4c ), (1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8a ), (4,5‐dichloro‐1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8b ) and (1‐methyl‐3‐benzylbenzimidazole‐2‐ylidene) silver(I) acetate ( 8c ) respectively. The four NHC‐precursors 3a–c, 7c and four NHC–silver complexes 4a–c and 8c were characterized by single crystal X‐ray diffraction. The preliminary antibacterial activity of all the compounds was studied against Gram‐negative bacteria Escherichia coli, and Gram‐positive bacteria Staphylococcus aureus using the qualitative Kirby‐Bauer disc‐diffusion method. All NHC–silver complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 4 to 12 mm at the highest amount used, while the NHC‐precursors showed significantly lower activity. In addition, all NHC–silver complexes underwent preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 and showed medium to high cytotoxicity with IC₅₀ values ranging from 53 ( ± 8) to 3.2 ( ± 0.6) µM. Copyright © 2010 John Wiley & Sons, Ltd.     

用聚乙二醇简便合成3-取代-1, 2, 3, 4-四氢吡啶并[3, 2-d]嘧啶-2, 4-二酮

用聚乙二醇作为可溶性聚合物载体和相转移催化剂高效简单的合成了1, 2, 3, 4-四氢吡啶并[3, 2-d]嘧啶类化合物。该合成路线为聚乙二醇与2, 3-吡啶二酸酐反应生成聚乙二醇支载的单酯1,接着1被转化成相应的聚乙二醇支载的酰基叠氮2,2经Curtius重排,与胺加成并同时关环给出目标产物,其总产率为84%-88%。     

PEG‐4000‐promoted palladium‐catalyzed N‐allylation in water: aminonaphthalene as an example

An environmentally friendly, efficient catalytic process using palladium associated with ligands in a PEG4000–water system leading to N‐allylation was described in this study. PEG‐4000 was found to improve the palladium‐catalyzed allylic amination of allylic acetates with aminonaphthalenes and gave overall good to high yields of the corresponding N‐allylic aminonaphthalenes. Copyright © 2012 John Wiley & Sons, Ltd.     

Macromolecular Organization of Poly(L‐lactide)‐block‐Polyoxyethylene into Bio‐Inspired Nano‐Architectures

Block copolymers create various types of nano‐structures, e. g., spheres, rods, cubes, and lamellae. This review discloses the dynamic macromolecular organization of block copolymers comprising poly(L ‐lactide) (PLLA) and poly(oxyethylene) (PEG) that allows to simulate elaborate biological systems. The block copolymers, AB‐ (PLLA‐PEG) and ABA‐type (PLLA‐PEG‐PLLA), are synthesized by ordinary lactide polymerization to have a controlled block length. They are dispersed into an aqueous medium to prepare nano‐scale particles, consisting of hydrophobic PLLA and hydrophilic PEG in the core and shell, respectively. Then, the particles are placed on a flat substrate by the casting method. The particles are detected as discoids by AFM, having shrunk with loss of water. Heat‐treatment of these particles at 60°C (above T_g of PLLA) gives rise to a collapse into small fragments, which then aggregate into bands with nano‐size width and thickness. The PLLA‐PEG bands align parallel to each other, while the PLLA‐PEG‐PLLA bands form a characteristic network resembling the neuron system created in animal tissue. As analyzed by TEM diffraction, each is composed of α‐crystal of PLLA whose c‐axis (molecular axis) is perpendicular to the substrate surface. Based on this fact, a doubly twisted chain structure of PLLA is proposed in addition to a plausible mechanism for the self‐organization of the block copolymers. Derivatives of the PLLA‐PEG block copolymers can form far more interesting nano‐architectures. An equimolar mixture of enantiomeric copolymers, PLLA‐PEG‐PLLA and PDLA‐PEG‐PDLA, forms a hydrogel that is thermo‐responsive. The terminal‐modified poly(L ‐lactide)‐block‐polyoxyethylene monocinnamate (PLLA‐PEG‐C) forms a highly stabilized nanofiber by the photo‐reaction of the cinnamates placed in the outer layer of the nanobands.     

Triptycene‐Based Chiral and meso‐N‐Heterocyclic Carbene Ligands and Metal Complexes

Based on 1‐amino‐4‐hydroxy‐triptycene, new saturated and unsaturated triptycene‐NHC (N‐heterocyclic carbene) ligands were synthesized from glyoxal‐derived diimines. The respective carbenes were converted into metal complexes [(NHC)MX] (M=Cu, Ag, Au; X=Cl, Br) and [(NHC)MCl(cod)] (M=Rh, Ir; cod=1,5‐cyclooctadiene) in good yields. The new azolium salts and metal complexes suffer from limited solubility in common organic solvents. Consequently, the introduction of solubilizing groups (such as 2‐ethylhexyl or 1‐hexyl by O‐alkylation) is essential to render the complexes soluble. The triptycene unit infers special steric properties onto the metal complexes that enable the steric shielding of selected areas close to the metal center. Next, chiral and meso‐triptycene based N‐heterocyclic carbene ligands were prepared. The key step in the synthesis of the chiral ligand is the Buchwald–Hartwig amination of 1‐bromo‐4‐butoxy‐triptycene with (1S,2S)‐1,2‐diphenyl‐1,2‐diaminoethane, followed by cyclization to the azolinium salt with HC(OEt)₃. The analogous reaction with meso‐1,2‐diphenyl‐1,2‐diaminoethane provides the respective meso‐azolinium salt. Both the chiral and meso‐azolinium salts were converted into metal complexes including [(NHC)AuCl], [(NHC)RhCl(cod)], [(NHC)IrCl(cod)], and [(NHC)PdCl(allyl)]. An in situ prepared chiral copper complex was tested in the enantioselective borylation of α,β‐unsaturated esters and found to give an excellent enantiomeric ratio (er close to 90:10).     

Radical trans‐Hydroboration of Alkynes with N‐Heterocyclic Carbene Boranes

Hydroboration of internal alkynes with N‐heterocyclic carbene boranes (NHC‐boranes) occurs to provide stable NHC (E)‐alkenylboranes upon thermolysis in the presence of di‐tert‐butyl peroxide. The E isomer results from an unusual trans‐hydroboration, and the E/Z selectivity is typically high (90:10 or greater). Evidence suggests that this hydroboration occurs by a radical‐chain reaction involving addition of an NHC‐boryl radical to an alkyne to give a β‐NHC‐borylalkenyl radical. Ensuing hydrogen abstraction from the starting NHC‐borane provides the product and returns the starting NHC‐boryl radical. Experiments suggest that the observed trans‐selectivity results from kinetic control in the hydrogen‐transfer reaction.     

Engineering a Cu‐MOF Nano‐Catalyst by using Post‐Synthetic Modification for the Preparation of 5‐Substituted 1H‐Tetrazoles

A new nano scale Cu‐MOF has been obtained via post‐synthetic metalation by immersing a Zn‐MOF as a template in DMF solutions of copper(II) salts. The Cu‐MOF serves as recyclable nano‐catalyst for the preparation of 5‐substituted 1H‐tetrazoles via [3 + 2] cycloaddition reaction of various nitriles and sodium azide in a green medium (PEG). The post‐synthetic metalated MOF were characterized by FT‐IR spectroscopy, powder X‐ray diffraction (PXRD), atomic absorption spectroscopy (AAS), and energy dispersive X‐ray spectroscopy (EDX) techniques. The morphology and size of the nano‐catalyst were determined by field emission scanning electron microscopy (FE‐SEM).